Fortradol

Package leaflet: Information for the patient

FORTRADOL 50 mg/1 ml solution for injection, 100 mg/2 ml solution for injection

Tramadol hydrochloride
Please read 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 other people, 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, contact your doctor or pharmacist.

Contents of this leaflet

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

1. What FORTRADOL is and what it is used for

Tramadol, the active substance of FORTRADOL, is an analgesic (pain reliever) belonging to the opioid class and acts on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
FORTRADOL is used for the treatment of moderate to severe pain of various types and causes, as well as pain caused by diagnostic and surgical procedures.

2. What you should know before using FORTRADOL

Do not use FORTRADOL

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6);
• in acute alcohol, sedative, opioid, or other psychotropic drug poisoning (medicines acting on mood and emotions);
• if you are currently taking or have taken monoamine oxidase inhibitors (MAO inhibitors) within the last 14 days prior to treatment with Fortradol (see "Other medicines and Fortradol");
• if you have epilepsy and your seizures are not adequately controlled by therapy;
• as a substitute in drug detoxification therapy.

Warnings and precautions
Sleep-related breathing disorders
Fortradol may cause sleep-related breathing disorders, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels).
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 observes these symptoms, contact your doctor, who may consider reducing the dose.

Talk to your doctor or pharmacist before using Fortradol:

• if you suffer from depression and are taking antidepressants, because some of them may interact with tramadol (see "Other medicines and Fortradol");
• if you think you may be misusing other painkillers (opioids);
• if you have disturbances of consciousness (if you feel faint);
• if you are in shock (cold sweats may be a sign);
• if you have increased intracranial pressure (possible after head trauma or brain diseases);
• if you have breathing difficulties;
• if you have a tendency to epilepsy or seizures, as the risk of an attack may increase;
• if you suffer from liver or kidney diseases.

There is a small but possible risk that you may develop the so-called serotonin syndrome, which may occur after taking tramadole together with certain antidepressants or tramadol as monotherapy.
Contact your doctor immediately if you experience any of the symptoms associated with this serious syndrome (see section 4 "Possible side effects").
Seizures have been reported in patients taking tramadol at recommended doses. The risk may increase when tramadol doses exceed the recommended levels, particularly beyond the daily maximum dose of 400 mg.
Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These symptoms may indicate adrenal insufficiency (low cortisol levels). If you experience these symptoms, contact your doctor, who will decide whether hormonal replacement is needed.

Tolerance, physical and psychological dependence
This medicine contains tramadol, a medicine belonging to the opioid class.
Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient becomes accustomed to its use, a phenomenon known as tolerance). Repeated use of Fortradol may also lead to abuse and physical and psychological dependence, with a consequent risk of potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged use.
In case of physical or psychological dependence, you may feel unable to control the amount of medicine you need or how often you need to take it.
The risk of developing physical or psychological dependence varies from person to person. The risk of developing dependence on Fortradol may be higher if:

• you or a family member has a history of alcohol, prescription medicine, or illegal drug abuse or dependence ("dependence");
• you are a smoker;
• you have had mood disorders (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs while taking Fortradol, you may have developed physical or psychological dependence:

• You need to take the medicine for longer than recommended by your doctor;
• You need to take a higher dose than recommended;
• You use the medicine for reasons other than those for which it was prescribed, e.g., to "stay calm" or "help sleep";
• You have repeatedly tried, but failed, to stop or control the use of the medicine;
• You feel unwell when you stop taking the medicine and feel better when you take it again ("withdrawal effects").

If you notice any of these signs, consult your doctor to evaluate the most appropriate treatment plan for you, including when it is appropriate to discontinue treatment and how to do so safely (see section 3, "If you stop taking Fortradol").
In patients with a tendency to medicine abuse or who are dependent on medicines, Fortradol should be taken only for short periods and under strict medical supervision.
Tramadol is metabolized in the liver by an enzyme. Some people have a variation in this enzyme, which may lead to different effects in them. Some people may not get sufficient pain relief, while others may experience severe adverse effects. If you notice any of the following adverse effects, you must stop taking this medicine and contact a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, feeling unwell or malaise, constipation, loss of appetite.

Children and adolescents
Use in children with respiratory problems
Tramadol is not recommended in children with respiratory problems, as symptoms of tramadol toxicity may be worse in these children.

Other medicines and FORTRADOL
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Fortradol must not be taken together with MAO inhibitors (some medicines used for depression).
The intensity and duration of the analgesic effect of Fortradol may be reduced if you are taking medicines containing:

• carbamazepine (for epileptic seizures);
• pentazocine, nalbuphine, or buprenorphine (analgesics);
• ondansetron (to prevent nausea). Your doctor will advise you whether and which doses of Fortradol you should take.

The risk of adverse effects increases if you are taking:

• other analgesics such as morphine and codeine (even when taken for cough), and alcohol together with Fortradol. You may feel drowsy or weak. In such cases, consult your doctor.
• the concomitant use of Fortradol and sedative or sleep medicines (e.g., benzodiazepines) increases the risk of sedation, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are possible. However, if your doctor prescribes Fortradol 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 dosing 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 such symptoms occur.
• medicines that may cause seizures (fits), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take Fortradol at the same time. Your doctor will tell you whether Fortradol is suitable for you.
• certain antidepressants; tramadol may interact with these medicines and you may develop serotonin syndrome (see section 4 "Possible side effects").
• coumarin anticoagulants (medicines that thin the blood), such as warfarin, together with Fortradol. The effect of these medicines on blood clotting may be affected, leading to bleeding.
• gabapentin or pregabalin for the treatment of epilepsy or nerve pain (neuropathic pain).

FORTRADOL with food and alcohol
Do not drink alcohol during treatment with Fortradol, as its effect may be enhanced.
Food intake does not affect the action of Fortradol.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
There is limited information on the safety of tramadol in pregnant women. Therefore, if you are pregnant, you should not use Fortradol injectable solution. Chronic use during pregnancy may lead to withdrawal symptoms in newborns.

Breastfeeding
Tramadol is excreted in breast milk. Therefore, you should not take Fortradol more than once during breastfeeding, or alternatively, if you take Fortradol more than once, you must stop breastfeeding. Ask your doctor for advice.
There is limited data on the effects of Fortradol on fertility. Post-marketing data do not suggest an effect of tramadol on fertility.

Driving and using machines
Fortradol may cause drowsiness, dizziness, and vision problems (blurred vision). If you feel your ability to react is impaired, do not drive vehicles or operate machinery requiring steady support.

Fortradol injectable solution contains less than 1 mmol (23 mg) of sodium per ml, i.e., essentially "sodium-free".

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

3. How to use FORTRADOL

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment and at regular intervals during treatment, your doctor will discuss with you what to expect from using Fortradol, when and for how long you should take it, when to contact your doctor, and when to stop taking it (see also section 2).
The dosage should be determined based on the intensity of pain and your individual sensitivity to pain. Generally, the lowest effective dose that relieves pain should be used. A daily dose of up to 8 ml of Fortradol injectable solution (equivalent to 8 vials of 50 mg or 4 vials of 100 mg, corresponding to 400 mg of tramadol hydrochloride) is usually sufficient, unless your doctor has given you different instructions.
Unless otherwise prescribed by your doctor, the usual dose is:
Adults and adolescents over 12 years of age:
Inject 1 or 2 ml (equivalent to 50 or 100 mg of tramadol hydrochloride) according to the intensity of pain, every 4–6 hours.
Children over 1 year of age:
The usual single dose is 1–2 mg of tramadol hydrochloride per kg of body weight. The lowest effective dose that relieves pain should be used. Daily doses must not exceed 8 mg of active substance per kg of body weight or 400 mg of active substance.
Elderly patients:
In elderly patients (over 75 years of age), elimination of tramadol may be delayed. If this applies to you, your doctor may advise you to increase the interval between doses.
Patients with severe hepatic or renal insufficiency/dialysis:
Fortradol must not be used by patients with severe hepatic and/or renal insufficiency. In cases of mild or moderate insufficiency, your doctor may advise you to increase the interval between doses.

How and when to administer FORTRADOL injectable solution
Fortradol injectable solution should be administered slowly, either intravenously (usually in the arm) or intramuscularly (typically in the buttock) or subcutaneously. Fortradol injectable solution may be diluted in a suitable infusion solution and administered intravenously.

Incompatibilities of FORTRADOL injectable solution
Fortradol injectable solution must not be diluted in injectable or infusion solutions containing:
diclofenac, piroxicam, indomethacin, phenylbutazone, diazepam, flunitrazepam, midazolam, nitroglycerin.

Instructions for use
Fortradol injectable solution is supplied in breakable ampoules. The ampoule has a scored break line. To open:

1. Hold the ampoule with the tip pointing upwards
2. Snap off the tip by pulling downwards

How long should you use Fortradol
Do not use Fortradol longer than necessary. If long-term treatment is required, your doctor will monitor you at regular, short intervals (and may temporarily interrupt therapy if needed) to determine whether you should continue treatment and at what dose.
If you feel that the analgesic effect of Fortradol is too strong or too weak, consult your doctor or pharmacist.

If you use more FORTRADOL than you should
If you have accidentally received an extra dose, this should not cause adverse effects. You may continue administering the medicine as prescribed.
After very high doses, the following may occur: pinpoint pupils, vomiting, drop in blood pressure, rapid heartbeat, collapse, disturbances of consciousness up to coma (deep unconsciousness), epileptic seizures, and breathing difficulties up to respiratory arrest. In such cases, call your doctor immediately.

If you forget to use FORTRADOL
If Fortradol injectable solution has not been administered, pain is likely to return. Do not administer a double dose to make up for the missed dose; continue treatment as instructed.

If you stop using FORTRADOL
If you stop or discontinue treatment too early, pain is likely to return.
If you wish to discontinue treatment due to adverse effects, consult your doctor.
Do not stop taking this medicine abruptly unless instructed by your doctor. If you intend to stop taking the medicine, discuss this first with your doctor, especially if you have been taking it for a long time. Your doctor will advise you when and how to stop, which may involve gradually reducing the dose to minimize the risk of developing unnecessary adverse effects (withdrawal symptoms).
Generally, discontinuation symptoms do not occur when stopping treatment with Fortradol.
However, in rare cases, some individuals who have taken Fortradol for a prolonged period may feel unwell when stopping abruptly.
They may:

• feel agitated, anxious, nervous, or weak
• be hyperactive, have difficulty sleeping, or experience stomach or intestinal disturbances
• experience panic attacks, hallucinations, unusual sensations such as itching, tingling, numbness, or ringing in the ears (tinnitus)
• experience other rare, unusual symptoms of the central nervous system (CNS), such as confusion, delusion, altered perception of self (depersonalization), altered perception of reality (derealization), and feelings of persecution (paranoia).
  If you experience any of these symptoms after stopping Fortradol, consult your doctor.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Consult a doctor immediately if you experience symptoms of an allergic reaction such as

• swelling of the face, tongue and/or throat
• difficulty swallowing
• hives
• difficulty breathing.

Other possible side effects are:
Very common (may affect more than 1 in 10 people)

• nausea
• dizziness

Common (may affect less than 1 in 10 people)

• headache, drowsiness
• vomiting, constipation, dry mouth
• sweating (hyperhidrosis)
• fatigue

Uncommon (may affect less than 1 in 100 people)

• effects on the heart and blood circulation (palpitations, fast heartbeat, feeling faint or collapse). These side effects may particularly occur in patients in an upright position or undergoing physical exertion
• feeling the need to vomit (nausea), stomach discomfort (sensation of pressure in the stomach, bloating), diarrhoea
• skin reactions (itching, rashes)

Rare (may affect less than 1 in 1,000 people)

• allergic reactions (e.g. difficulty breathing, shortness of breath, skin swelling) and shock (circulatory failure)
• slow heartbeat
• increase in blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, epileptic seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• epileptic seizures have occurred mainly with high doses of tramadol or when tramadol was taken together with other medicines that may provoke seizures
• changes in appetite
• hallucinations, confusion, sleep disturbances, delirium, anxiety and nightmares. Psychological symptoms may occur after treatment with Fortradol, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as mood changes (mainly elevated mood, sometimes irritable mood), changes in activity (usually decreased or suppressed, sometimes increased) and reduced cognitive and sensory perception (changes in senses and emotional recognition ability, which may lead to impaired judgment)
• drug dependence. When treatment is abruptly discontinued, withdrawal symptoms may occur (see "If you stop treatment with Fortradol").
• vision problems, excessive dilation of the pupils (mydriasis), constriction of the pupils (miosis)
• slow breathing, shortness of breath (dyspnoea). If recommended doses are exceeded, or if other medicines that reduce brain function are taken simultaneously, breathing may become slower
• worsening of asthma, although it has not been established whether this may have been caused by tramadol
• muscle weakness
• difficulty or pain when urinating, reduced urine output (dysuria)

Very rare (may affect less than 1 in 10,000 people)

• increased liver enzyme levels
• slow breathing

Frequency not known (frequency cannot be estimated from the available data)

• decrease in blood sugar levels (hypoglycaemia)
• hiccups
• sleep-related breathing disorders (central sleep apnoea syndrome)
• serotonin syndrome, which may present as changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2 "What you need to know before taking Fortradol").

In the literature, cases of SIADH (syndrome of inappropriate antidiuretic hormone secretion) and hyponatraemia (low sodium levels in the blood) have been reported, although a causal relationship with tramadol has not been established.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 Fortradol

Keep out of the sight and reach of children.
Store this medicine in a safe and secure place, where others cannot access it.
It may cause serious harm or be fatal to people for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the carton and label. The expiry date refers to the last day of the month. This medicine does not require any special storage conditions.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What FORTRADOL contains
The active substance is tramadol hydrochloride.
FORTRADOL 100 mg/2 ml injectable solution: each vial contains 100 mg of tramadol hydrochloride.
FORTRADOL 50 mg/1 ml injectable solution: each vial contains 50 mg of tramadol hydrochloride.
The other components are: sodium acetate, water for injectable preparations.

Description of the appearance of FORTRADOL injectable solution and contents of the pack
Colourless, clear solution.
FORTRADOL injectable solution is contained in clear glass vials, in packs of 5 vials.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Alfasigma S.p.A. – Via Ragazzi del ’99, n. 5 – 40133 Bologna (BO)

Manufacturer responsible for batch release
Farmaceutici Formenti S.p.A. – Via di Vittorio, 2 – 21040 Origgio (VA)
Grünenthal GmbH Aachen, Germany

Patient Information Leaflet

FORTRADOL 150 mg prolonged-release tablets, 200 mg prolonged-release tablets

Tramadol hydrochloride
Please read 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, consult 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, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist.

Contents of this leaflet

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

1. What FORTRADOL is and what it is used for

Tramadol, the active substance in Fortradol, is an analgesic (pain reliever) belonging to the opioid class, and acts on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Fortradol is used to treat moderate to severe pain.

2. What you should know before taking FORTRADOL

Do not take Fortradol

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6);
• in cases of acute alcohol, sedative, opioid, or other psychotropic drug intoxication (medications that affect mood and emotions);
• if you are currently taking MAO inhibitors (certain medications used to treat depression) or have taken them within the last 14 days prior to treatment with Fortradol (see "Other medicines and Fortradol");
• if you have epilepsy and your seizures are not adequately controlled by therapy;
• as a substitute in drug detoxification therapy.

Warnings and precautions
Sleep-related breathing disorders
Fortradol may cause sleep-related breathing disorders, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels during sleep).
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 observes these symptoms, contact your doctor, who may consider reducing the dose.
Talk to your doctor or pharmacist before taking Fortradol:

• if you suffer from depression and are taking antidepressants, because some of them may interact with tramadol (see "Other medicines and Fortradol");
• if you think you might misuse other painkillers (opioids);
• if you have disturbances of consciousness (if you feel faint);
• if you are in a state of shock (cold sweats may be a sign);
• if you have increased intracranial pressure (possible after head trauma or brain diseases);
• if you have difficulty breathing;
• if you have a tendency to epilepsy or seizures, as the risk of an attack may increase;
• if you have liver or kidney disease.

There is a small risk that you may develop the so-called serotonin syndrome, which may occur after taking tramadol together with certain antidepressants or tramadol as monotherapy.
Contact your doctor immediately if you experience any of the symptoms associated with this serious condition (see section 4 "Possible side effects").
Seizures have been reported in patients taking tramadol at recommended doses. The risk may increase when tramadol doses exceed the recommended levels, beyond the daily maximum dose of 400 mg.
Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These symptoms may indicate adrenal insufficiency (low cortisol levels). If you experience these symptoms, contact your doctor, who will decide whether hormonal replacement is needed.
Tolerance, physical and psychological dependence
This medicine contains tramadol, a medicine belonging to the opioid class.
Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient becomes accustomed to its use, a phenomenon known as tolerance). Repeated use of Fortradol may also lead to abuse and physical and psychological dependence, with a consequent risk of potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged use.
In case of physical or psychological dependence, you may feel unable to control the amount of medicine you need or how often you need to take it.
The risk of developing physical or psychological dependence varies from person to person. The risk of developing physical or psychological dependence on Fortradol may be higher if:

• you or a family member has a history of alcohol, prescription medicine, or illegal drug abuse or dependence ("addiction");
• you are a smoker;
• you have had mood disorders (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental illnesses. If you notice any of the following signs while taking Fortradol, you may have developed physical or psychological dependence:
• You need to take the medicine for longer than recommended by your doctor;
• You need to take a higher dose than recommended;
• You use the medicine for reasons other than those for which it was prescribed, e.g., to "stay calm" or "help sleep";
• You have repeatedly tried, but failed, to stop or control the use of the medicine;
• You feel unwell when you stop taking the medicine and feel better when you take it again ("withdrawal effects"). If you notice any of these signs, consult your doctor to evaluate the most appropriate treatment plan for you, including when and how to safely discontinue treatment (see section 3, "If you stop taking Fortradol").

In patients with a tendency to medicine abuse or who are dependent on medicines, Fortradol should be taken only for short periods and under strict medical supervision.
Tramadol is metabolized in the liver by an enzyme. Some people have a variation in this enzyme, which may lead to different effects in them. Some people may not achieve sufficient pain relief, while others may experience serious adverse effects. If you notice any of the following adverse effects, you must stop taking this medicine and contact a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, feeling unwell or malaise, constipation, loss of appetite.
Children and adolescents
Use in children with respiratory problems
Tramadol is not recommended in children with respiratory problems, as symptoms of tramadol toxicity may be worse in these children.
Other medicines and Fortradol
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Fortradol must not be taken together with MAO inhibitors (certain medicines used for depression).
The intensity and duration of the analgesic effect of Fortradol may be reduced if you are taking medicines containing:

• carbamazepine (for epileptic seizures);
• pentazocine, nalbuphine, or buprenorphine (analgesics);
• ondansetron (to prevent nausea). Your doctor will inform you whether and what dose of Fortradol you should take.

The risk of adverse effects increases if you are taking:

• other analgesics such as morphine and codeine (even when taken for cough), and alcohol together with Fortradol. You may feel drowsy or weak. In such cases, consult your doctor.
• concomitant use of Fortradol and sedative or sleep medicines (e.g., benzodiazepines) increases the risk of sedation, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are possible. However, if your doctor prescribes Fortradol together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor. Inform your doctor about all sedative medicines you are taking and follow the dosage recommendations carefully. It may be helpful to inform friends or family members about the signs and symptoms listed above. Contact your doctor if such symptoms occur.
• medicines that may cause seizures (fits), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take Fortradol at the same time. Your doctor will tell you whether Fortradol is suitable for you.
• certain antidepressants; Fortradol may interact with these medicines and you may develop serotonin syndrome (see section 4 "Possible side effects").
• coumarin anticoagulants (medicines that thin the blood), such as warfarin, together with Fortradol. The effect of these medicines on blood clotting may be affected, and bleeding may occur.
• gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

Fortradol with food and alcohol
Do not drink alcohol during treatment with Fortradol, as its effect may be enhanced.
Food intake does not affect the effect of Fortradol.
Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
There is limited information on the safety of tramadol in pregnant women. Therefore, if you are pregnant, you should not use Fortradol.
Chronic use during pregnancy may lead to withdrawal symptoms in newborns.
Breastfeeding
Tramadol is excreted in breast milk. For this reason, you should not take Fortradol more than once during breastfeeding, or alternatively, if you take Fortradol more than once, you must stop breastfeeding.
There is limited data on the effects of Fortradol on fertility. Post-marketing data do not suggest an effect of tramadol on fertility.
Driving and using machines
Fortradol may cause drowsiness, dizziness, and vision problems (blurred vision). If you feel your ability to react is impaired, do not drive vehicles or operate machinery or tools that require a steady hand.
Fortradol prolonged-release tablets contain lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
For athletes:
Using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take FORTRADOL

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Before starting treatment and at regular intervals during treatment, your doctor will discuss with you what
to expect from using Fortradol, when and for how long you should take it, when you should contact your
doctor, and when you should stop taking it (see also section 2).
The dosage should be based on the intensity of pain and your individual sensitivity to pain. In general, the
lowest effective dose that relieves pain should be taken. Do not take more than 400 mg of tramadol
hydrochloride per day unless your doctor has instructed you otherwise.
Unless otherwise prescribed by your doctor, the usual dose is:
Adults and adolescents over 12 years of age
One prolonged-release tablet of Fortradol 150 mg twice daily (equivalent to 300 mg of tramadol
hydrochloride per day), preferably in the morning and evening.
One prolonged-release tablet of Fortradol 200 mg twice daily (equivalent to 400 mg of tramadol
hydrochloride per day), preferably in the morning and evening.
If necessary, your doctor may prescribe a different and more appropriate dose of Fortradol.
Use in children
Fortradol prolonged-release tablets are not suitable for children under 12 years of age.
Elderly patients
In elderly patients (over 75 years of age), elimination of tramadol may be delayed. If this applies to you,
your doctor may advise you to increase the interval between doses.
Patients with severe hepatic or renal impairment / dialysis
Patients with severe hepatic and/or renal impairment must not take Fortradol. In cases of mild or moderate
impairment, your doctor may advise you to increase the interval between doses.
How and when to take Fortradol
Fortradol prolonged-release tablets are to be taken orally.
Always swallow Fortradol prolonged-release tablets whole, without dividing or chewing, with a sufficient
amount of liquid, preferably in the morning and evening. You may take the tablets either with or without
food.
How long to take Fortradol
Do not take Fortradol for longer than necessary. If long-term treatment is required, your doctor will
monitor you at regular, short intervals (and may temporarily interrupt therapy if needed) to determine
whether you should continue treatment and at which dose.
If you feel that the analgesic effect of Fortradol is too strong or too weak, consult your doctor or pharmacist.
If you take more Fortradol than you should
If you accidentally take an extra dose, this should not cause harmful effects. You may continue taking the
medicine as prescribed.
After taking very high doses, the following may occur: pinpoint pupils, vomiting, drop in blood pressure,
rapid heartbeat, collapse, disturbances of consciousness up to coma (deep unconsciousness), epileptic
seizures, and breathing difficulties up to respiratory arrest. In such cases, contact your doctor immediately.
If you forget to take Fortradol
If you forget to take your tablets, your pain may return. Do not double the dose to make up for the missed
dose; simply continue taking the tablets as before.
If you stop taking Fortradol
If you stop or discontinue treatment too early, your pain is likely to return.
If you wish to stop treatment due to side effects, consult your doctor.
Do not stop taking this medicine abruptly unless instructed by your doctor. If you intend to stop taking the
medicine, especially if you have been taking it for a long time, discuss this first with your doctor. Your doctor
will advise you when and how to stop, which may involve gradually reducing the dose to minimize the
likelihood of developing unnecessary adverse effects (withdrawal symptoms).
Generally, discontinuation symptoms do not occur when stopping treatment with Fortradol.
However, in rare cases, some individuals who have taken Fortradol for a certain period of time may feel unwell
when they stop abruptly.
Specifically, they may:

• feel restless, anxious, nervous, or weak
• be overactive, have difficulty sleeping, or experience stomach or intestinal disturbances
• experience panic attacks, hallucinations, unusual sensations such as itching, tingling, numbness, or ringing in the ears (tinnitus)
• experience other very rare CNS symptoms such as confusion, delusions, altered perception of self (depersonalization), altered perception of reality (derealization), and feelings of persecution (paranoia). If you experience any of these symptoms after stopping Fortradol, contact your doctor.

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.
Contact a doctor immediately if you experience symptoms of an allergic reaction such as

• swelling of the face, tongue and/or throat
• difficulty swallowing
• hives
• difficulty breathing.

Other possible side effects are:
Very common (may affect more than 1 in 10 people)

• nausea
• dizziness

Common (may affect less than 1 in 10 people)

• headache, drowsiness
• vomiting, constipation, dry mouth
• sweating (hyperhidrosis)
• fatigue

Uncommon (may affect less than 1 in 100 people)

• effects on the heart and blood circulation (palpitations, fast heartbeat, feeling faint or collapse). These side effects may occur particularly in patients in an upright position or during physical exertion
• feeling the need to vomit (nausea), stomach discomfort (feeling of pressure in the stomach, bloating), diarrhoea
• skin reactions (itching, rashes)

Rare (may affect less than 1 in 1,000 people)

• allergic reactions (e.g. difficulty breathing, shortness of breath, skin swelling) and shock (circulatory failure)
• slow heartbeat
• increase in blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, epileptic seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• epileptic seizures have occurred mainly with high doses of tramadol or when tramadol was taken together with other medicines that may cause seizures
• changes in appetite
• hallucinations, confusion, sleep disorders, delirium, anxiety and nightmares. Psychological symptoms may occur after treatment with Fortradol, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as changes in mood (mainly good mood, in some cases irritable mood), changes in activity (usually decreased or suppressed, sometimes increased), and reduced cognitive and sensory perception (changes in senses and emotional recognition ability, which may lead to impaired judgment)
• drug dependence. When treatment is stopped abruptly, withdrawal symptoms may occur (see "If you stop treatment with Fortradol")
• vision problems, excessive dilation of the pupils (mydriasis), constriction of the pupils (miosis)
• slow breathing, shortness of breath (dyspnoea). If recommended doses are exceeded, or if medicines that reduce brain function are taken simultaneously, breathing may become slower
• worsening of asthma; however, it has not been established whether this could have been caused by tramadol
• muscle weakness
• difficulty or pain when urinating, reduced urine output (dysuria)

Very rare (may affect less than 1 in 10,000 people)

• increased liver enzyme values
• slow breathing

Frequency not known (frequency cannot be estimated from the available data)

• decrease in blood sugar levels (hypoglycaemia)
• hiccups
• sleep-related breathing disorders (central sleep apnoea syndrome)
• serotonin syndrome, which may present as changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2 "What you need to know before taking Fortradol").

In the literature, cases of SIADH (syndrome of inappropriate antidiuretic hormone secretion) and hyponatraemia (low sodium levels in the blood) have been reported, although a causal relationship with tramadol has not been established.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please contact your doctor, pharmacist, or nurse. You may 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 FORTRADOL

Keep out of sight and reach of children.
Store this medicine in a safe and secure place, where other people cannot access it.
It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month. This medicine does not require any special storage conditions.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Fortradol contains
The active substance is tramadol hydrochloride.
Fortradol prolonged-release tablets 150 mg
One tablet contains 150 mg of tramadol hydrochloride.
The other components are: core: microcrystalline cellulose, hypromellose 100,000 mPa·s, magnesium stearate, anhydrous colloidal silica; coating: hypromellose 6 mPa·s, lactose monohydrate (see section 2 “Fortradol contains lactose”), macrogol 6000, propylene glycol, talc, titanium dioxide (E 171), quinoline yellow (E 104), iron oxide red (E 172).
Fortradol prolonged-release tablets 200 mg
One tablet contains 200 mg of tramadol hydrochloride.
The other components are: core: microcrystalline cellulose, hypromellose 100,000 mPa·s, magnesium stearate, anhydrous colloidal silica; coating: hypromellose 6 mPa·s, lactose monohydrate (see section 2 “Fortradol contains lactose”), macrogol 6000, propylene glycol, talc, titanium dioxide (E 171), quinoline yellow (E 104), iron oxide red (E 172), iron oxide brown (E 172).

Description of the appearance of Fortradol and package contents
Fortradol 150 mg prolonged-release tablets are round, biconvex, light orange in colour, with the code T2 engraved on one side and the logo  on the other.
Fortradol 200 mg prolonged-release tablets are round, biconvex, dark orange in colour, with the code T3 engraved on one side and the logo  on the other.
Fortradol 150 mg and 200 mg prolonged-release tablets are supplied in blister packs and sold in boxes containing 10 tablets.

Marketing Authorization Holder
Alfasigma S.p.A. – Via Ragazzi del ’99, n. 5 – 40133 Bologna (BO)
Manufacturer
Farmaceutici Formenti S.p.A. - Via di Vittorio, 2 - 21040 Origgio (VA)
Grünenthal GmbH – Zieglerstrasse 6 Aachen (Germany)

Patient Information Leaflet: Information for the patient
FORTRADOL 50 mg hard capsules
Tramadol hydrochloride
Read this leaflet carefully before 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, inform your doctor or pharmacist.

Contents of this leaflet

1. What FORTRADOL is and what it is used for
2. What you need to know before taking FORTRADOL
3. How to take FORTRADOL
4. Possible side effects
5. How to store FORTRADOL
6. Package contents and other information

1. What FORTRADOL is and what it is used for

Tramadol, the active substance of Fortradol, is an analgesic (painkiller) belonging to the opioid class and acts on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Fortradol is used for the treatment of moderate to severe pain of various types and causes, as well as for pain caused by diagnostic and surgical procedures.

2. What you need to know before taking FORTRADOL

Do not take Fortradol

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6);
• in cases of acute alcohol, hypnotic, opioid or other psychotropic drug intoxication (medicines acting on mood and emotions);
• if you are currently taking MAO inhibitors (certain medicines used to treat depression) or have taken them within the last 14 days prior to starting Fortradol treatment (see "Other medicines and Fortradol");
• if you have epilepsy and your seizures are not adequately controlled by therapy;
• as a substitute in drug detoxification therapy.

Warnings and precautions
Sleep-related breathing disorders
Fortradol may cause sleep-related breathing disorders, such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels).
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 observes these symptoms, contact your doctor, who may consider reducing the dose.

Talk to your doctor or pharmacist before taking Fortradol:

• if you suffer from depression and are taking antidepressants, as some of them may interact with tramadol (see "Other medicines and Fortradol");
• if you think you may be overusing other painkillers (opioids);
• if you have disturbances of consciousness (feeling faint);
• if you are in a state of shock (cold sweats may be a sign);
• if you have increased intracranial pressure (possible after head trauma or brain diseases);
• if you have breathing difficulties;
• if you have a tendency to epilepsy or seizures, as the risk of seizure may increase;
• if you have liver or kidney disease.

There is a small but possible risk that you may develop the so-called serotonin syndrome, which may occur after taking tramadol together with certain antidepressants or tramadol used alone.
Contact your doctor immediately if you experience any of the symptoms associated with this serious syndrome (see section 4 "Possible side effects").
Seizures have been reported in patients taking tramadol at recommended doses. The risk may increase when tramadol doses exceed the recommended levels, particularly beyond the daily maximum dose of 400 mg.
Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure may indicate adrenal insufficiency (low cortisol levels). If you experience these symptoms, contact your doctor, who will decide whether hormone replacement is needed.

Tolerance, physical and psychological dependence
This medicine contains tramadol, a medicine belonging to the opioid class.
Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient becomes accustomed to it, a phenomenon known as tolerance). Repeated use of Fortradol may also lead to abuse and physical and psychological dependence, with a consequent risk of potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged use.
In case of physical or psychological dependence, you may feel unable to control the amount of medicine you need or how often you take it.
The risk of developing physical or psychological dependence varies from person to person. The risk of developing dependence on Fortradol may be higher if:

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

If you notice any of the following signs while taking Fortradol, you may have developed physical or psychological dependence:

• You need to take the medicine for longer than recommended by your doctor;
• You need to take a higher dose than recommended;
• You use the medicine for reasons other than those for which it was prescribed, e.g. to "stay calm" or "help sleep";
• You have repeatedly tried, but failed, to stop or control the use of the medicine;
• You feel unwell when you stop taking the medicine and feel better when you take it again ("withdrawal effects").

If you notice any of these signs, consult your doctor to evaluate the most appropriate treatment plan for you, including when and how to safely discontinue treatment (see section 3, "If you stop taking Fortradol"). In patients with a tendency to medicine abuse or who are dependent on medicines, Fortradol should only be taken for short periods and under strict medical supervision.

Tramadol is metabolized in the liver by an enzyme. Some people have a variation in this enzyme, which may lead to different effects. Some people may not get sufficient pain relief, while others may experience serious adverse effects. If you notice any of the following adverse effects, you must stop taking this medicine and contact a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, feeling unwell or malaise, constipation, loss of appetite.

Children and adolescents
Use in children with respiratory problems
Tramadol is not recommended in children with respiratory problems, as symptoms of tramadol toxicity may be worse in these children.

Other medicines and FORTRADOL
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicine.
Fortradol must not be taken together with MAO inhibitors (certain medicines used for depression).
The strength and duration of the analgesic effect of Fortradol may be reduced if you are taking medicines containing

• carbamazepine (for epileptic seizures);
• pentazocine, nalbuphine or buprenorphine (analgesics);
• ondansetron (to prevent nausea). Your doctor will inform you whether and which doses of Fortradol you should take.

The risk of adverse effects increases if you are taking

• other analgesics such as morphine and codeine (even when taken for cough), and alcohol together with Fortradol. You may feel drowsy or weak. In such cases, consult your doctor.
• concomitant use of Fortradol and sedative or sleep medicines (e.g. benzodiazepines) increases the risk of sedation, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when no other treatment options are available. However, if your doctor prescribes Fortradol together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor. Inform your doctor about all sedative medicines you are taking and follow carefully the dosage recommendations provided. It may be helpful to inform friends or relatives about the signs and symptoms listed above. Contact your doctor if such symptoms occur.
• medicines that may cause seizures (fits), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take Fortradol at the same time. Your doctor will advise whether Fortradol is suitable for you.
• certain antidepressants: tramadol may interact with these medicines and you may develop serotonin syndrome (see section 4 "Possible side effects").
• coumarin anticoagulants (medicines that thin the blood), such as warfarin, together with Fortradol. The effect of these medicines on blood clotting may be altered, leading to bleeding.
• gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

FORTRADOL with food and alcohol
Do not drink alcohol during treatment with Fortradol, as its effects may be enhanced.
Food intake does not affect the action of Fortradol.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
There is limited information on the safety of tramadol in pregnant women. Therefore, if you are pregnant, you should not use Fortradol. Chronic use during pregnancy may lead to withdrawal symptoms in newborns.
Breastfeeding
Tramadol is excreted in breast milk. Therefore, you should not take Fortradol more than once during breastfeeding; alternatively, if you take Fortradol more than once, you must stop breastfeeding.
There is limited data on the effects of Fortradol on fertility. Post-marketing data do not suggest an effect of tramadol on fertility.

Driving and using machines
Fortradol may cause drowsiness, dizziness and vision problems (blurred vision). If you feel that your ability to react is impaired, do not drive vehicles or operate machinery, or use tools or devices requiring steady support.

Fortradol capsules contain less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially "sodium-free".

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

3. How to take FORTRADOL

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment and at regular intervals during treatment, your doctor will discuss with you what to expect from using Fortradol, when and for how long you should take it, when to contact your doctor, and when to stop taking it (see also section 2).
The dose should be adjusted according to the intensity of pain and your individual sensitivity to pain. Generally, the lowest effective dose that relieves pain should be used. Do not take more than 400 mg (8 capsules) of tramadol hydrochloride per day, unless your doctor has given you different instructions.
Unless otherwise prescribed by your doctor, the usual dose is:
Adults and adolescents over 12 years of age:
One or two capsules (equivalent to 50 or 100 mg of tramadol hydrochloride) every 4–6 hours.
Use in children
Fortradol 50 mg capsules are not recommended for children under 12 years of age.
Elderly patients
In elderly patients (over 75 years of age), elimination of tramadol may be delayed. If this applies to you, your doctor may advise you to increase the interval between doses.
Patients with severe hepatic or renal impairment / dialysis
Fortradol must not be taken by patients with severe hepatic and/or renal impairment. In cases of mild or moderate impairment, your doctor may advise you to increase the interval between doses.
How and when to take Fortradol
Fortradol 50 mg capsules are for oral use. Swallow the capsules whole, not divided or chewed, with a sufficient amount of liquid, preferably in the morning and evening. You may take the capsules either with or without food.
How long to take Fortradol
Do not take Fortradol for longer than necessary. If long-term treatment is required, your doctor will monitor you at regular, frequent intervals (and may temporarily interrupt therapy if necessary) to determine whether you should continue treatment and at what dose.
If you feel that the analgesic effect of Fortradol is too strong or too weak, consult your doctor or pharmacist.
If you take more Fortradol than you should
If you accidentally take an extra dose, this should not cause adverse effects. You may continue taking the medicine as prescribed.
After ingestion of very high doses, the following may occur: pinpoint pupils, vomiting, drop in blood pressure, rapid heartbeat, collapse, disturbances of consciousness up to coma (deep unconsciousness), epileptic seizures, and breathing difficulties up to respiratory arrest. In such cases, contact your doctor immediately.
If you forget to take Fortradol
If you forget to take Fortradol, your pain may return. Do not double the dose to make up for a missed dose. Simply continue taking the capsules as before.
If you stop taking Fortradol
If you stop or discontinue treatment too early, your pain may return.
If you wish to stop treatment due to side effects, consult your doctor.
Do not stop taking this medicine abruptly, unless instructed by your doctor. If you intend to stop taking the medicine, especially if you have been taking it for a long time, discuss this first with your doctor. Your doctor will advise you on when and how to stop, which may involve gradually reducing the dose to minimize the risk of developing unnecessary adverse effects (withdrawal symptoms).
Generally, discontinuation symptoms do not occur when stopping treatment with Fortradol.
However, in rare cases, some people who have taken Fortradol for a prolonged period may feel unwell when stopping abruptly.
Specifically, they may:

• feel restless, anxious, nervous, or weak
• be hyperactive, have difficulty sleeping, or experience stomach or intestinal disturbances
• have panic attacks, hallucinations, unusual sensations such as itching, tingling, numbness, and ringing in the ears (tinnitus)
• experience other very rare CNS symptoms such as confusion, delusions, altered perception of self (depersonalization), altered perception of reality (derealization), and feelings of persecution (paranoia).

If you experience any of these symptoms after stopping Fortradol, consult your doctor.
If you have any questions about the use of 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.
Consult a doctor immediately if you experience symptoms of an allergic reaction such as

• swelling of the face, tongue and/or throat
• difficulty swallowing
• hives
• difficulty breathing.

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

• nausea
• dizziness

Common (may affect less than 1 in 10 people)

• headache, drowsiness
• vomiting, constipation, dry mouth
• sweating (hyperhidrosis)
• fatigue

Uncommon (may affect less than 1 in 100 people)

• effects on the heart and blood circulation (palpitations, rapid heartbeat, feeling of faintness or collapse). These side effects may occur particularly in patients in an upright position or undergoing physical exertion
• feeling the need to vomit (nausea), stomach discomfort (feeling of pressure in the stomach, bloating), diarrhoea
• skin reactions (itching, rashes)

Rare (may affect less than 1 in 1000 people)

• allergic reactions (e.g. difficulty breathing, shortness of breath, skin swelling) and shock (circulatory failure)
• slow heartbeat
• increased blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, epileptic seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• epileptic seizures have occurred mainly with high doses of tramadol or when tramadol was taken together with other medicines that may cause seizures
• changes in appetite
• hallucinations, confusion, sleep disturbances, delirium, anxiety and nightmares. Psychological symptoms may occur after treatment with Fortradol, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as changes in mood (mainly elevated mood, in some cases irritable mood), changes in activity (usually decrease or suppression, sometimes increase), and reduced cognitive and sensory perception (changes in senses and emotional recognition ability, which may lead to impaired judgment)
• drug dependence. When treatment is stopped abruptly, withdrawal symptoms may occur (see "If you stop treatment with Fortradol")
• vision problems, excessive dilation of the pupils (mydriasis), constriction of the pupils (miosis)
• slow breathing, shortness of breath (dyspnoea). If recommended doses are exceeded, or if medicines that reduce brain function are taken concomitantly, breathing may become slower
• worsening of asthma; however, it has not been established whether this could be caused by tramadol
• muscle weakness
• difficulty or pain when urinating, reduced urine output (dysuria)

Very rare (may affect less than 1 in 10,000 people)

• increased liver enzyme levels
• slow breathing

Frequency not known (frequency cannot be estimated from the available data)

• decrease in blood sugar levels (hypoglycaemia)
• hiccups
• sleep-related breathing disorders (central sleep apnoea syndrome)
• serotonin syndrome, which may present as changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2 "What you need to know before taking Fortradol").

Cases of SIADH (syndrome of inappropriate antidiuretic hormone secretion) and hyponatraemia (low sodium levels in the blood) have been reported in the literature, although a causal relationship with tramadol has not been established.
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 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 FORTRADOL

Keep out of the sight and reach of children.
Store this medicine in a safe and secure place, where others cannot access it.
It may cause serious harm or be fatal to people for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the month.
Store below 30 °C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Fortradol contains
The active substance is tramadol hydrochloride.
One capsule contains 50 mg of tramadol hydrochloride.
The other components are: microcrystalline cellulose, sodium carboxymethylstarch (type A), magnesium stearate,
anhydrous colloidal silica; the empty capsule shell contains: gelatin, titanium dioxide (E171), yellow iron oxide (E172).
Description of the appearance of Fortradol 50 mg hard capsules and pack contents
Hard, shiny, yellow, oblong capsules.
Pack size: 20 hard capsules.
Marketing Authorization Holder
Alfasigma S.p.A. – Via Ragazzi del ’99, n. 5 – 40133 Bologna (BO), Italy
Responsible manufacturer for batch release
Farmaceutici Formenti S.p.A. – Via Di Vittorio, 2 – 21040 Origgio (VA), Italy
Grünenthal GmbH, Zieglerstrasse 6, Aachen – Germany
Package leaflet: information for the patient
FORTRADOL 100 mg/ml oral drops, solution
Tramadol hydrochloride
10 ml bottle with dropper
Please read 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 effect, including those not listed in this leaflet, contact your doctor or pharmacist.

Contents of this leaflet

1. What FORTRADOL is and what it is used for
2. What you need to know before taking FORTRADOL
3. How to take FORTRADOL
4. Possible side effects
5. How to store FORTRADOL
6. Package contents and other information

1. What FORTRADOL is and what it is used for

Tramadol – the active substance in Fortradol – is an analgesic (pain reliever) belonging to the opioid class and acts on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Fortradol is used to treat moderate to severe pain of various types and causes, as well as pain caused by diagnostic and surgical procedures.

2. What you should know before taking FORTRADOL

Do not take Fortradol solution:

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6);
• in acute alcohol, sedative, opioid analgesic, or other psychotropic drug poisoning (medicines that affect mood and emotions);
• if you are currently taking or have taken monoamine oxidase inhibitors (MAO inhibitors—some medicines used to treat depression) within the last 14 days before starting Fortradol treatment (see "Other medicines and Fortradol");
• if you have epilepsy and your seizures are not adequately controlled by therapy;
• as a substitute in drug detoxification therapy.

Warnings and precautions
Sleep-related breathing disorders
Fortradol may cause sleep-related breathing disorders, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels).
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 observes these symptoms, contact your doctor, who may consider reducing the dose.
Consult your doctor or pharmacist before taking Fortradol:

• if you suffer from depression and are taking antidepressants, as some of them may interact with tramadol (see "Other medicines and Fortradol");
• if you think you may misuse other painkillers (opioids);
• if you have disturbances of consciousness (feeling faint);
• if you are in shock (cold sweats may be a sign);
• if you have increased intracranial pressure (possible after head trauma or brain diseases);
• if you have difficulty breathing;
• if you have a predisposition to epilepsy or seizures, as the risk of an attack may increase;
• if you have liver or kidney disease.

There is a small risk that you may develop the so-called serotonin syndrome, which may occur after taking tramadol together with certain antidepressants or tramadol used as monotherapy.
Contact your doctor immediately if you experience any of the symptoms associated with this serious syndrome (see section 4 "Possible side effects").
Seizures have been reported in patients taking tramadol at recommended doses. The risk may increase when tramadol doses exceed the recommended levels, particularly beyond the daily maximum dose of 400 mg.
Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These symptoms may indicate adrenal insufficiency (low cortisol levels). If you experience these symptoms, contact your doctor, who will decide whether hormonal replacement is needed.

Tolerance, physical and psychological dependence
This medicine contains tramadol, a medicine belonging to the opioid class.
Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient becomes accustomed to it—a phenomenon known as tolerance). Repeated use of Fortradol may also lead to abuse and physical and psychological dependence, with a consequent risk of potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged use.
In case of physical or psychological dependence, you may feel unable to control the amount of medicine you need or how often you take it.
The risk of developing physical or psychological dependence varies from person to person. The risk of developing dependence on Fortradol may be higher if:

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

If you notice any of the following signs while taking Fortradol, you may have developed physical or psychological dependence:

• You need to take the medicine for longer than recommended by your doctor;
• You need to take a higher dose than recommended;
• You use the medicine for reasons other than those for which it was prescribed, e.g., to "stay calm" or "help sleep";
• You have repeatedly tried, but failed, to stop or control your use of the medicine;
• You feel unwell when you stop taking the medicine and feel better when you take it again ("withdrawal effects").

If you notice any of these signs, consult your doctor to evaluate the most appropriate treatment plan for you, including when and how to safely discontinue treatment (see section 3, "If you stop taking Fortradol").

In patients with a tendency to misuse medicines or who are dependent on medicines, Fortradol should be taken only for short periods and under strict medical supervision.
Tramadol is metabolized in the liver by an enzyme. Some people have variations in this enzyme, which may lead to different effects in them. Some people may not get sufficient pain relief, while others may experience serious adverse effects. If you notice any of the following adverse effects, you must stop taking this medicine and contact a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, feeling unwell or malaise, constipation, or loss of appetite.

Children and adolescents
Use in children with respiratory problems
Tramadol is not recommended in children with respiratory problems, as symptoms of tramadol toxicity may be worse in these children.

Other medicines and Fortradol
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Fortradol must not be taken together with MAO inhibitors (some medicines used for depression).
The intensity and duration of the analgesic effect of Fortradol may be reduced if you are taking medicines containing:

• carbamazepine (for epileptic seizures);
• pentazocine, nalbuphine, or buprenorphine (analgesics);
• ondansetron (to prevent nausea). Your doctor will inform you whether and which dose of Fortradol you should take.

The risk of adverse effects increases if you are taking:

• other analgesics such as morphine and codeine (including codeine used for cough), and alcohol together with Fortradol. You may feel drowsy or weak. In such cases, consult your doctor.
• concomitant use of Fortradol and sedatives or sleeping medicines (e.g., benzodiazepines) increases the risk of sedation, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when no other treatment options are available. However, if your doctor prescribes Fortradol together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor. Inform your doctor about all sedative medicines you are taking and carefully follow the dosage recommendations provided. It may be helpful to inform friends or relatives about the signs and symptoms listed above. Contact your doctor if such symptoms occur.
• medicines that may cause seizures (fits), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take Fortradol at the same time. Your doctor will tell you whether Fortradol is suitable for you.
• certain antidepressants, as Fortradol may interact with these medicines and may cause serotonin syndrome (see section 4 "Possible side effects").
• coumarin anticoagulants (medicines that thin the blood), such as warfarin, together with Fortradol. The effect of these medicines on blood clotting may be affected, and bleeding may occur.
• gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

Fortradol with food and alcohol
Do not drink alcohol during treatment with Fortradol, as its effect may be enhanced.
Food intake does not affect the action of Fortradol.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
There is limited information on the safety of tramadol in pregnant women. Therefore, if you are pregnant, you should not use Fortradol oral drops solution with dropper. Chronic use during pregnancy may lead to withdrawal symptoms in newborns.
Breastfeeding
Tramadol is excreted in breast milk. Therefore, you should not take Fortradol more than once during breastfeeding; alternatively, if you take Fortradol more than once, you must stop breastfeeding.
There is limited data on the effects of Fortradol on fertility. Post-marketing data do not suggest an effect of tramadol on fertility.

Driving and using machines
Fortradol may cause drowsiness, dizziness, and vision problems (blurred vision). If you feel your ability to react is impaired, do not drive vehicles or operate machinery, or use tools or devices requiring steady support.

Fortradol 100 mg/ml oral drops solution contains sucrose, macrogol glycerol hydroxystearate, propylene glycol, and sodium.
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine, as it contains sucrose.
If Fortradol 100 mg/ml oral drops solution is used chronically (e.g., for two weeks or longer), it may be harmful to teeth.
Fortradol 100 mg/ml oral drops solution contains macrogol glycerol hydroxystearate, a derivative of castor oil, which may cause gastrointestinal disturbances and diarrhea.
Fortradol 100 mg/ml oral drops solution contains 150 mg of propylene glycol per ml.
Fortradol 100 mg/ml oral drops solution contains less than 1 mmol (23 mg) of sodium per ml, i.e., essentially "sodium-free."

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

3. How to take FORTRADOL

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment and at regular intervals during treatment, your doctor will discuss with you what to expect from using Fortradol, when and for how long you should take it, when to contact your doctor, and when to stop taking it (see also section 2).
The dosage should be determined based on the intensity of pain and your individual sensitivity to pain. Generally, the lowest effective dose that relieves pain should be taken. Do not take more than 160 drops per day (e.g. 8 doses of 20 drops each) (equivalent to 400 mg of tramadol hydrochloride) unless your doctor has given you different instructions. Unless otherwise prescribed by a physician, the usual dose is:
Adults and adolescents over 12 years of age:
20 to 40 drops (equivalent to 50 mg or 100 mg of tramadol hydrochloride), every 4–6 hours.
Use in children over 1 year of age
In children over 1 year of age, the single dose is 4–8 drops per 10 kg of body weight (1–2 mg of tramadol hydrochloride per kg of body weight). For more detailed information on dosing according to body weight, refer to the notes at the end of this leaflet.
The lowest dose that relieves pain should be taken. Daily doses must not exceed 8 mg of active substance per kg of body weight or 400 mg of active substance.
Elderly patients
In elderly patients (over 75 years), elimination of tramadol may be delayed. If this applies to you, your doctor may advise you to increase the time interval between doses.
Patients with severe hepatic or renal impairment / dialysis
Fortradol must not be taken by patients with severe hepatic and/or renal impairment. In cases of mild or moderate impairment, your doctor may advise you to increase the time interval between doses.
How and when to take Fortradol
Take Fortradol 100 mg/ml oral drops solution with sugar or a small amount of liquid.
For information on how to use the dropper, read the instructions at the end of this leaflet.
Food intake does not affect the effect of Fortradol.
How long to take Fortradol
Do not take Fortradol longer than necessary. If long-term treatment is required, your doctor will monitor you with frequent and regular check-ups (possibly including temporary interruption of therapy if needed) to determine whether you should continue treatment and at what dose.
If you feel that the analgesic effect of Fortradol is too strong or too weak, consult your doctor or pharmacist.
If you take more Fortradol than you should
If you accidentally take an extra dose, this should not cause adverse effects. You may continue taking the medicine as prescribed.
After taking very high doses, the following may occur: pinpoint pupils, vomiting, drop in blood pressure, rapid heartbeat, collapse, disturbances of consciousness up to coma (deep unconsciousness), epileptic seizures, and breathing difficulties up to respiratory arrest. In such cases, contact your doctor immediately.
If you forget to take Fortradol
If you forget to take the oral solution, pain may return. Do not double the dose to make up for the missed dose; simply continue taking the medicine as before.
If you stop taking Fortradol
If you stop or discontinue treatment too early, pain may return.
If you wish to stop treatment due to side effects, consult your doctor.
Do not stop taking this medicine abruptly unless instructed by your doctor. If you intend to stop taking the medicine, especially after long-term use, discuss this first with your doctor. Your doctor will advise you when and how to stop, which may involve gradually reducing the dose to minimize the risk of developing unnecessary side effects (withdrawal symptoms).
Generally, discontinuation symptoms do not occur when stopping treatment with Fortradol.
However, in rare cases, some individuals who have taken Fortradol for a prolonged period may feel unwell if they stop abruptly.
They may:

• feel restless, anxious, nervous, or weak
• be overactive, have difficulty sleeping, or experience stomach or intestinal disturbances
• experience panic attacks, hallucinations, unusual sensations such as itching, tingling, numbness, or ringing in the ears (tinnitus)
• experience other very rare central nervous system (CNS) symptoms such as confusion, delusions, altered perception of self (depersonalization), altered perception of reality (derealization), and feelings of persecution (paranoia). If you experience any of these symptoms after stopping Fortradol, contact your doctor.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Consult a doctor immediately if you experience symptoms of an allergic reaction such as

• swelling of the face, tongue and/or throat
• difficulty swallowing
• hives
• difficulty breathing.

Other possible side effects are:
Very common (may affect more than 1 in 10 people)

• nausea
• dizziness

Common (may affect less than 1 in 10 people)

• headache, drowsiness
• vomiting, constipation, dry mouth
• sweating (hyperhidrosis)
• fatigue

Uncommon (may affect less than 1 in 100 people)

• effects on the heart and blood circulation (palpitations, fast heartbeat, feeling of faintness or collapse). These side effects may particularly occur in patients in an upright position or undergoing physical exertion
• urge to vomit (nausea), stomach discomfort (feeling of pressure in the stomach, bloating), diarrhoea
• skin reactions (itching, rashes)

Rare (may affect less than 1 in 1000 people)

• allergic reactions (e.g. difficulty breathing, breathlessness, skin swelling) and shock (circulatory failure)
• slow heartbeat
• increase in blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• seizures have occurred especially with high doses of tramadol or when tramadol was taken together with other medicines that may provoke seizures
• changes in appetite
• hallucinations, confusion, sleep disturbances, delirium, anxiety and nightmares. Psychological symptoms may occur after treatment with Fortradol, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as changes in mood (mainly elevated mood, sometimes irritable mood), changes in activity (usually decreased or suppressed, sometimes increased) and reduced cognitive and sensory perception (changes in senses and emotional recognition ability, which may lead to impaired judgment)
• drug dependence. When treatment is stopped abruptly, withdrawal symptoms may occur (see "If you stop treatment with Fortradol").
• vision problems, excessive dilation of the pupils (mydriasis), constriction of the pupils (miosis)
• slow breathing, shortness of breath (dyspnoea). If recommended doses are exceeded, or if other medicines that reduce brain function are taken simultaneously, breathing may become slower
• worsening of asthma; however, it has not been established whether this could have been caused by tramadol
• muscle weakness
• difficulty or pain when urinating, reduced urine output (dysuria)

Very rare (may affect less than 1 in 10,000 people)

• increased liver enzyme levels
• slow breathing

Frequency not known (frequency cannot be estimated from the available data)

• decrease in blood sugar levels (hypoglycaemia)
• hiccups
• sleep-related breathing disorders (central sleep apnoea syndrome)
• serotonin syndrome, which may present as changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2 "What you need to know before taking Fortradol").

Cases of SIADH (syndrome of inappropriate antidiuretic hormone secretion) and hyponatraemia (low sodium levels in the blood) have been reported in the literature, although a causal relationship with tramadol has not been established.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 Fortradol

Keep out of the sight and reach of children.
Store this medicine in a safe and secure place where others cannot access it.
It may cause serious harm or be fatal to people for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the carton and label. The expiry date refers to the last day of the month. This medicine does not require any special storage conditions.
The medicine should be used within 12 months after first opening the bottle; after this period, any remaining medicine must be discarded.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Fortradol contains
The active substance is tramadol hydrochloride.
Each ml of solution contains 100 mg of tramadol hydrochloride (one drop contains 2.5 mg of tramadol).
The other components are: sucrose (0.2 g/ml solution), propylene glycol, glycerol, sodium cyclamate,
sodium saccharin, potassium sorbate, macrogol glycerol hydroxystearate, peppermint flavor, anise flavor, purified water.
Description of the appearance of Fortradol 100 mg/ml oral drops solution and contents of the pack
Fortradol 100 mg/ml oral drops solution is a clear, slightly viscous, pale yellow liquid.
The solution is contained in an amber glass bottle and contains 10 ml of solution.
Marketing Authorization Holder
Alfasigma S.p.A. – Via Ragazzi del ’99, n. 5 – 40133 Bologna (BO)
Manufacturer responsible for batch release
Farmaceutici Formenti S.p.A. – Via di Vittorio, 2 – 21040 Origgio (VA)
Grünenthal GmbH – Aachen, Germany
Instructions for use of Fortradol 100 mg/ml oral drops solution
The Fortradol bottle is supplied in a tamper-evident package. The carton is sealed, and the bottle has a security ring. Only if the carton, its perforation, and the bottle’s ring are intact can you be certain that the contents have not been tampered with.
If the packaging is damaged, please inform your pharmacist.
Note regarding the content quantity
Due to differences in wall and bottom thickness of the bottle, the liquid level may vary by a few millimeters in the sealed packaging of Fortradol 100 mg/ml oral drops solution.
The bottle of Fortradol 100 mg/ml oral drops solution has a child-resistant closure. To open, press firmly down on the cap and unscrew it. After use, close the cap tightly.
To dispense the drops, hold the bottle in an upright position with the opening

facing downward. Gently tap the bottom of the bottle with a finger until the first drop appears.
For dosing instructions, refer to section 3 “HOW TO TAKE FORTRADOL 100 mg/ml ORAL DROPS SOLUTION”.
Tramadol hydrochloride content in the drops:

Number of drops	Tramadol hydrochloride
1 drop	2.5 mg
5 drops	12.5 mg
10 drops	25 mg
15 drops	37.5 mg
20 drops	50 mg
25 drops	62.5 mg
30 drops	75 mg
35 drops	87.5 mg
40 drops	100 mg

Note on Fortradol oral drops solution dosage in children over 1 year of age
Dosage table according to body weight in children (see also “HOW TO TAKE
FORTRADOL 100 mg/ml oral drops solution”).

Approximate age	Body weight	Number of drops per single dose (1-2 mg/kg)
1 year	10 kg	4-8
3 years	15 kg	6-12
6 years	20 kg	8-16
9 years	30 kg	12-24
11 years	45 kg	18-36

Patient Information Leaflet

FORTRADOL 100 mg prolonged-release tablets

Tramadol hydrochloride
Please read 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, consult 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, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist.

Contents of this leaflet

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

1. What FORTRADOL is and what it is used for

Tramadol, the active substance in Fortradol, is an analgesic (pain reliever) belonging to the opioid class and acts on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Fortradol is used for the treatment of moderate to severe pain of various types and causes, as well as for pain caused by diagnostic and surgical procedures.

2. What you need to know before taking FORTRADOL

Do not take Fortradol

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6);
• in acute alcohol intoxication, or intoxication with sleeping pills, painkillers, or other psychotropic medicines (medicines that affect mood and emotions);
• if you are currently taking MAO inhibitors (certain medicines used to treat depression), or if you have taken them within the last 14 days before starting treatment with Fortradol (see “Other medicines and Fortradol”);
• if you have epilepsy and your seizures are not adequately controlled by treatment;
• as a substitute in drug detoxification therapy.

Warnings and precautions
Sleep-related breathing disorders
Fortradol may cause sleep-related breathing disorders, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels during sleep).
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 the dose.

Talk to your doctor or pharmacist before taking Fortradol:

• if you suffer from depression and are taking antidepressants, as some of them may interact with tramadol (see “Other medicines and Fortradol”);
• if you think you may be misusing other painkillers (opioids);
• if you have disturbances of consciousness (feeling faint);
• if you are in shock (cold sweats may be a sign);
• if you have increased intracranial pressure (possible after head trauma or brain diseases);
• if you have difficulty breathing;
• if you have a tendency to epilepsy or seizures, as the risk of an attack may increase;
• if you have liver or kidney disease.

There is a small but possible risk that you may develop the so-called serotonin syndrome, which may occur after taking tramadol together with certain antidepressants or tramadol used alone.
Contact your doctor immediately if you experience any of the symptoms associated with this serious condition (see section 4 “Possible side effects”).
Seizures have been reported in patients taking tramadol at recommended doses. The risk may increase when tramadol doses exceed the recommended levels, beyond the daily maximum dose of 400 mg.
Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These symptoms may indicate adrenal insufficiency (low cortisol levels). If you experience these symptoms, contact your doctor, who will decide whether hormone replacement therapy is needed.

Tolerance, physical and psychological dependence
This medicine contains tramadol, a medicine belonging to the opioid class.
Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient becomes accustomed to its use, a phenomenon known as tolerance). Repeated use of Fortradol may also lead to abuse and physical and psychological dependence, with a consequent risk of potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged use.
In case of physical or psychological dependence, you may feel unable to control the amount of medicine you need or how often you take it.
The risk of developing physical or psychological dependence varies from person to person. The risk of developing dependence on Fortradol may be higher if:

• you or a family member has a history of alcohol, prescription medicine, or illegal drug abuse or dependence (“addiction”);
• you are a smoker;
• you have had mood disorders (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs while taking Fortradol, you may have developed physical or psychological dependence:

• You need to take the medicine for longer than recommended by your doctor;
• You need to take a higher dose than recommended;
• You use the medicine for reasons other than those for which it was prescribed, for example, to “stay calm” or “help sleep”;
• You have repeatedly tried, but failed, to stop or control the use of the medicine;
• You feel unwell when you stop taking the medicine and feel better when you take it again (“withdrawal effects”).

If you notice any of these signs, consult your doctor to evaluate the most appropriate treatment plan for you, including when it is appropriate to stop treatment and how to do so safely (see section 3, “If you stop taking Fortradol”).

In patients with a tendency to misuse medicines or who are dependent on medicines, Fortradol should be taken only for short periods and under strict medical supervision.
Tramadol is metabolized in the liver by an enzyme. Some people have a variation in this enzyme, which may lead to different effects in them. Some people may not get sufficient pain relief, while others may experience serious adverse effects. If you notice any of the following adverse effects, you must stop taking this medicine and contact a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, feeling unwell or malaise, constipation, loss of appetite.

Children and adolescents
Use in children with respiratory problems
Tramadol is not recommended in children with respiratory problems, as symptoms of tramadol toxicity may be worse in these children.

Other medicines and FORTRADOL
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Fortradol must not be taken together with MAO inhibitors (certain medicines used for depression).
The intensity and duration of the analgesic effect of Fortradol may be reduced if you are taking medicines containing

• carbamazepine (for epileptic seizures);
• pentazocine, nalbuphine, or buprenorphine (analgesics);
• ondansetron (to prevent nausea). Your doctor will inform you whether and what doses of Fortradol you should take.

The risk of adverse effects increases if you are taking

• other analgesics such as morphine and codeine (even when taken for cough), and alcohol together with Fortradol. You may feel drowsy or weak. In such cases, consult your doctor.
• concomitant use of Fortradol and sedative or sleeping medicines (e.g., benzodiazepines) increases the risk of sedation, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are possible. However, if your doctor prescribes Fortradol 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 dosage 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 such symptoms occur.
• medicines that may cause seizures (fits), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take Fortradol at the same time. Your doctor will tell you whether Fortradol is suitable for you.
• certain antidepressants; Fortradol may interact with these medicines and you may develop serotonin syndrome (see section 4 “Possible side effects”).
• coumarin anticoagulants (medicines that thin the blood), such as warfarin, together with Fortradol. The effect of these medicines on blood clotting may be affected, and bleeding may occur.
• gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

Fortradol with food and alcohol
Do not drink alcohol during treatment with Fortradol, as its effect may be enhanced.
Food intake does not affect the effect of Fortradol.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
There is limited information on the safety of tramadol in pregnant women. Therefore, if you are pregnant, you should not use Fortradol. Chronic use during pregnancy may lead to withdrawal symptoms in newborns.

Breastfeeding
Tramadol is excreted in breast milk. For this reason, you should not take Fortradol more than once during breastfeeding, or alternatively, if you take Fortradol more than once, you must stop breastfeeding.
There is limited data on the effects of Fortradol on fertility. Post-marketing data do not suggest an effect of tramadol on fertility.

Driving and using machines
Fortradol may cause drowsiness, dizziness, and vision problems (blurred vision). If you feel that your ability to react is affected, do not drive vehicles or operate machinery, or use tools or instruments that require secure handling.

Fortradol 100 mg prolonged-release tablets contain lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine, which contains lactose.

For those engaged in sports:
Using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take FORTRADOL

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Before starting treatment and at regular intervals during treatment, your doctor will discuss with you what
to expect from the use of Fortradol, when and for how long you should take it, when you should contact
your doctor, and when you should stop taking it (see also section 2).
The dose should be determined based on the intensity of pain and your individual sensitivity to pain. In
general, the lowest effective dose that relieves pain should be taken. Do not take more than 400 mg of
tramadol hydrochloride per day unless your doctor has instructed otherwise.
Unless otherwise prescribed by your doctor, the usual dose is:
Adults and adolescents over 12 years of age:
One prolonged-release tablet of Fortradol 100 mg twice daily (equivalent to 200 mg of
tramadol hydrochloride per day), preferably in the morning and evening.
Your doctor may prescribe a different dose of Fortradol if necessary.
Use in children
Fortradol 100 mg prolonged-release tablets are not recommended for children under 12 years
of age.
Elderly patients
In elderly patients (over 75 years of age), elimination of tramadol may be delayed. If this applies to you,
your doctor may advise you to increase the interval between doses.
Patients with severe hepatic or renal impairment / dialysis
Patients with severe hepatic and/or renal impairment must not take Fortradol. In cases of mild or moderate
impairment, your doctor may advise you to increase the interval between doses.
How and when to take Fortradol
Fortradol 100 mg prolonged-release tablets are for oral use.
Swallow the tablets whole, without dividing or chewing, with a sufficient amount of liquid, preferably in the
morning or evening. You may take the tablets either with or without food.
How long to take Fortradol
Do not take Fortradol longer than necessary. If long-term treatment is required, your doctor will monitor you
at regular and frequent intervals (temporarily interrupting therapy if necessary) to determine whether you
should continue treatment and at which dose.
If you feel that the analgesic effect of Fortradol is too strong or too weak, consult your doctor or pharmacist.
If you take more Fortradol than you should
If you accidentally take an extra dose, this should not cause adverse effects. You may continue taking the
medicine as prescribed.
After taking very high doses, the following may occur: pinpoint pupils, vomiting, drop in blood pressure,
rapid heartbeat, collapse, disturbances of consciousness up to coma (deep unconsciousness),
seizures, and breathing difficulties up to respiratory arrest. In such cases, contact your doctor immediately.
If you forget to take Fortradol
If you forget to take Fortradol, your pain may return. Do not double the dose to make up for the missed
dose; simply continue taking the tablets as previously directed.
If you stop taking Fortradol
If you stop or discontinue treatment too early, your pain may return.
If you wish to stop treatment due to side effects, consult your doctor.
Do not stop taking this medicine abruptly unless instructed by your doctor. If you intend to stop taking the
medicine, discuss this with your doctor first, especially if you have been taking it for a long time. Your doctor
will advise you when and how to stop, which may involve gradually reducing the dose to minimize the
risk of developing unnecessary side effects (withdrawal symptoms).
Generally, discontinuation symptoms do not occur when stopping Fortradol.
However, in rare cases, some individuals who have taken Fortradol for a prolonged period may feel unwell
when stopping abruptly.
They may:

• feel restless, anxious, nervous, or weak
• be overactive, have difficulty sleeping, or experience stomach or intestinal disturbances
• experience panic attacks, hallucinations, unusual sensations such as itching, tingling, numbness, or ringing in the ears (tinnitus)
• experience other rare central nervous system (CNS) symptoms such as confusion, delusions, altered perception of self (depersonalization), altered perception of reality (derealization), and feelings of persecution (paranoia). If you experience any of these symptoms after stopping Fortradol, consult your doctor.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Contact a doctor immediately if you experience symptoms of an allergic reaction such as

• swelling of the face, tongue and/or throat
• difficulty swallowing
• hives
• difficulty breathing.

Other possible side effects are:
Very common (may affect more than 1 in 10 people)

• nausea
• dizziness

Common (may affect less than 1 in 10 people)

• headache, drowsiness
• vomiting, constipation, dry mouth
• sweating (hyperhidrosis)
• fatigue

Uncommon (may affect less than 1 in 100 people)

• effects on the heart and blood circulation (palpitations, fast heartbeat, feeling faint or collapse). These side effects may occur particularly in patients in an upright position or undergoing physical exertion
• feeling the need to vomit (nausea), stomach discomfort (feeling of pressure in the stomach, bloating), diarrhoea
• skin reactions (itching, rashes)

Rare (may affect less than 1 in 1,000 people)

• allergic reactions (e.g. difficulty breathing, shortness of breath, skin swelling) and shock (circulatory failure)
• slow heartbeat
• increase in blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, epileptic seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• epileptic seizures have occurred mainly with high doses of tramadol or when tramadol was taken together with other medicines that may provoke seizures
• changes in appetite
• hallucinations, confusion, sleep disturbances, delirium, anxiety and nightmares. Psychological symptoms may occur after treatment with Fortradol, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as mood changes (mainly euphoria, sometimes irritability), changes in activity (usually decreased or suppressed, sometimes increased), and reduced cognitive and sensory perception (changes in senses and emotional recognition ability, which may lead to impaired judgment)
• drug dependence. When treatment is stopped abruptly, withdrawal symptoms may occur (see “If you stop treatment with Fortradol”)
• vision problems, excessive dilation of the pupils (mydriasis), constriction of the pupils (miosis)
• slow breathing, shortness of breath (dyspnoea). If the recommended doses are exceeded, or if other medicines that reduce brain function are taken at the same time, breathing may become slower
• worsening of asthma; however, it has not been established whether this could have been caused by tramadol
• muscle weakness
• difficulty or pain when urinating, reduced urine output (dysuria)

Very rare (may affect less than 1 in 10,000 people)

• increased liver enzyme levels
• slow breathing

Frequency not known (frequency cannot be estimated from the available data)

• decrease in blood sugar levels (hypoglycaemia)
• hiccups
• breathing disorders related to sleep (central sleep apnoea syndrome)
• serotonin syndrome, which may present as changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2 “What you need to know before taking Fortradol”)

Cases of SIADH (syndrome of inappropriate antidiuretic hormone secretion) and hyponatraemia (low sodium levels in the blood) have been reported in the literature, although a causal relationship with tramadol has not been established.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting side effects can help provide more information on the safety of this medicine.

5. How to store FORTRADOL

Keep out of the sight and reach of children.
Store this medicine in a safe and secure place, where other people cannot access it.
It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the carton and on the blister. The expiry date refers to
the last day of the month.
This medicine does not require any special storage conditions.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Fortradol contains
The active substance is tramadol hydrochloride.
Each tablet contains 100 mg of tramadol hydrochloride.
The other components are: core: microcrystalline cellulose, hypromellose 100,000 mPa  S, colloidal anhydrous silica, magnesium stearate; coating: hypromellose 6 mPa  s, monohydrate lactose (see section 2 "Fortradol 100 mg prolonged-release tablets contain lactose"), macrogol 6000, propylene glycol, talc, titanium dioxide (E171).
Description of the appearance of Fortradol 100 mg prolonged-release tablets and pack contents
White, round tablets imprinted with the code T1 and the logo .
Pack size: 20 prolonged-release tablets.
Marketing Authorization Holder
Alfasigma S.p.A. – Via Ragazzi del ’99, n. 5 – 40133 Bologna (BO)
Manufacturer responsible for batch release
Farmaceutici Formenti S.p.A. - Via di Vittorio, 2 – 21040 Origgio (VA)
Grünenthal GmbH – Zieglerstrasse 6 - Aachen (Germany)