CONTRAMAL

Patient Information Leaflet

CONTRAMAL 100 mg prolonged-release tablets

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 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, contact your doctor or pharmacist.

Contents of this leaflet

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

1. What CONTRAMAL is and what it is used for

Tramadol – the active substance in Contramal 100 mg prolonged-release tablets – is an analgesic (for pain) belonging to the opioid class, acting on the central nervous system.
It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Contramal 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 CONTRAMAL

Do not take Contramal

• 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 that affect mood and emotions)
• if you are currently taking, or have taken within the last 14 days, MAO inhibitors (certain medicines used to treat depression) before starting treatment with Contramal (see "Other medicines and Contramal")
• if you have epilepsy and your seizures are not adequately controlled by therapy
• as a substitute in drug detoxification therapy.

Warnings and precautions
Talk to your doctor or pharmacist before taking Contramal if:

• you suffer from disturbances of consciousness (if you feel faint)
• you are in a state of shock (cold sweats may be a sign)
• you have increased intracranial pressure (possible after head trauma or brain diseases)
• you have breathing difficulties
• you have a tendency to epilepsy or seizures, as the risk of an attack may increase
• you suffer from liver or kidney diseases
• you have depression and are taking antidepressants, because some of them may interact with tramadol (see "Other medicines and Contramal"). 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 condition (see section 4 "Possible side effects").

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 Contramal 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 Contramal 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 Contramal, 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 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 Contramal").
For athletes: using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.
Sleep-related breathing disorders
Contramal contains an active ingredient belonging to the opioid group. Opioids may cause sleep-related breathing disorders, such as central sleep apnea (shallow breathing or breathing pauses during sleep) and sleep-related hypoxemia (low blood oxygen levels).
The risk of central sleep apnea is dose-dependent on opioids. Your doctor may consider reducing the total opioid dosage if central sleep apnea occurs.
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.
Contramal may lead to physical and psychological dependence. When Contramal is administered for long periods, its effect may decrease, thus requiring higher doses (development of tolerance). In patients with a tendency to medicine abuse or who are medicine-dependent, Contramal should be taken only for short periods and under strict medical supervision.
Inform your doctor if any of these problems occur during treatment with Contramal or have occurred previously.
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.
Contact your doctor if you experience any of the following symptoms while taking CONTRAMAL:
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.
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 Contramal
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Contramal must not be taken together with MAO inhibitors (certain medicines used for depression).
The intensity and duration of the analgesic effect of Contramal may be reduced if you are taking medicines containing:

• carbamazepine (for epileptic seizures)
• ondansetron (to prevent nausea). Your doctor will advise you whether and which doses of Contramal 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 Contramal. You may feel drowsy or weak. In such cases, consult your doctor.
• concomitant use of Contramal and sedatives 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 Contramal 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 the dosage recommendations provided carefully. 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 Contramal at the same time. Your doctor will advise you whether Contramal is suitable for you.
• certain antidepressants. Contramal may interact with these medicines and you may develop serotonin syndrome (see section 4 "Possible side effects").
• anticoagulant coumarins (medicines that thin the blood), such as warfarin, together with Contramal. 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).

Contramal with food, drinks and alcohol
Do not drink alcohol during treatment with Contramal, as its effect may be enhanced.
Food intake does not affect the action of Contramal.
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 Contramal. Chronic use during pregnancy may lead to withdrawal symptoms in newborns.
Breastfeeding
Tramadol is excreted in breast milk. Therefore, you should not take Contramal more than once during breastfeeding; alternatively, if you take Contramal more than once, you must stop breastfeeding.
There is limited data on the effects of Contramal on fertility.
Driving and using machines
Contramal may cause drowsiness, dizziness, and vision problems (blurred vision). If you feel that your ability to react is impaired, do not drive or operate vehicles or machinery requiring secure footing.
Contramal 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.

3. How to take CONTRAMAL

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 you can expect from using Contramal, 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 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 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 tablet of Contramal 100 mg prolonged-release twice daily (equivalent to 200 mg of tramadol hydrochloride per day), preferably in the morning and evening.
Your doctor may prescribe a different dosage of Contramal if necessary.
Children
Contramal 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 Contramal. In cases of mild or moderate impairment, your doctor may advise you to increase the interval between doses.
How and when to take Contramal 100 mg prolonged-release tablets
Contramal 100 mg prolonged-release tablets are for oral use.
Swallow the tablets whole, undivided and unchewed, with sufficient liquid, preferably in the morning or evening. You may take the tablets either with or without food.
How long to take Contramal
Do not take Contramal 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 dosage.
If you feel that the analgesic effect of Contramal is too strong or too weak, consult your doctor or pharmacist.
If you take more Contramal than you should
Taking an extra dose by mistake should not cause adverse effects. You may continue taking the medicine as prescribed.
However, 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 Contramal
If you forget to take Contramal, 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 Contramal
If you stop or discontinue treatment too early, your pain may return.
If you wish to stop 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, especially if you have been taking it for a long time, discuss this with your doctor first. Your doctor will advise you when and how to stop. This may involve gradually reducing the dose to minimize the risk of unnecessary adverse effects (withdrawal symptoms).
Generally, discontinuation symptoms do not occur when stopping treatment with Contramal.
However, in rare cases, some people who have taken Contramal for some time may feel unwell when stopping 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 rare central nervous system (CNS) symptoms such as confusion, depression, altered perception of self (depersonalization), altered perception of reality (derealization), and feelings of persecution (paranoia). If you experience any of these symptoms after stopping Contramal, 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 experiences 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, rapid 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 1000 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, slow breathing, seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• 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 Contramal, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as a change in mood (mainly elevated 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 judgment errors).

• drug dependence. When treatment is stopped abruptly, withdrawal symptoms may occur (see “If you stop taking Contramal”)
• 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

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

• decrease in blood sugar levels
• hiccups
• 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 Contramal”).

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

5. How to store CONTRAMAL

Keep this medicine 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 pack. 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Contramal 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, anhydrous colloidal silica, magnesium stearate; coating: hypromellose 6 mPa·s, lactose monohydrate (see section 2 “Contramal 100 mg prolonged-release tablets contain lactose”), macrogol 6000, propylene glycol, talc, titanium dioxide (E171).

Description of the appearance of Contramal 100 mg prolonged-release tablets and package contents
White, round tablets, marked with the code T1 and the logo .
Pack size: 20 prolonged-release tablets.

Marketing Authorization Holder
GRÜNENTHAL ITALIA S.r.l. – Via Vittor Pisani 16 - 20124 Milano, Italy

Responsible manufacturer for batch release
FARMACEUTICI FORMENTI S.p.A. - Via Di Vittorio, 2 – 21040 Origgio (VA), Italy
GRÜNENTHAL GmbH – Zieglerstrasse 6, 52078 Aachen, Germany

This leaflet was last updated on:

Patient Information Leaflet

CONTRAMAL 50 mg hard capsules

Tramadol hydrochloride
Please 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, consult 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 could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist.

Contents of this leaflet

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

1. What CONTRAMAL is and what it is used for

Tramadol – the active substance in Contramal – is an analgesic (for pain) belonging to the opioid class, acting on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Contramal 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 CONTRAMAL

Do not take CONTRAMAL

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6)
• in acute alcohol, hypnotics, opioids or other psychotropic drug poisoning (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 before starting treatment with Contramal (see "Other medicines and Contramal")
• if you have epilepsy and your seizures are not adequately controlled by therapy
• as a substitute in drug detoxification therapy.

Warnings and precautions
Talk to your doctor or pharmacist before taking Contramal if:

• you suffer from disturbances of consciousness (if you feel faint)
• you are in a state of shock (cold sweats may be a sign)
• you have increased intracranial pressure (possible after head trauma or brain diseases)
• you have breathing difficulties
• you have a tendency to epilepsy or seizures, as the risk of an attack may increase
• you suffer from liver or kidney disease
• you suffer from depression and are taking antidepressants, because some of them may interact with tramadol (see "Other medicines and Contramal"). 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 syndrome (see section 4 "Possible side effects").

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 Contramal 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.
If you develop physical or psychological dependence, you may feel unable to control the amount of medicine you need or how often you must take it.
The risk of developing physical or psychological dependence varies from person to person. The risk of developing physical or psychological dependence on Contramal 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 Contramal, 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 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 Contramal").
For athletes: using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.
Sleep-related breathing disorders
Contramal contains an active substance belonging to the opioid group. Opioids can cause sleep-related breathing disorders, such as central sleep apnea (shallow breathing or breathing pauses during sleep) and sleep-related hypoxemia (low blood oxygen levels).
The risk of central sleep apnea depends on the opioid dose. Your doctor may consider reducing the total opioid dosage if central sleep apnea occurs.
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 limit of 400 mg.
Contramal may lead to physical and psychological dependence. When Contramal is administered for a long time, its effect may decrease, thus requiring higher doses (development of tolerance). In patients with a tendency to medicine abuse or who are medicine-dependent, Contramal 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 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.
Contact your doctor if you experience any of the following symptoms while taking CONTRAMAL:
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 you need hormone replacement therapy.
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 Contramal
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Contramal must not be taken together with MAO inhibitors (certain medicines used for depression).
The intensity and duration of the analgesic effect of Contramal may be reduced if you are taking medicines containing:

• carbamazepine (for epileptic seizures)
• ondansetron (to prevent nausea). Your doctor will inform you whether and which doses of Contramal 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 Contramal. You may feel drowsy or faint. In such cases, consult your doctor.
• concomitant use of Contramal 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 Contramal 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 relatives about the signs and symptoms listed above. Contact your doctor if these 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 Contramal at the same time. Your doctor will tell you whether Contramal is suitable for you.
• certain antidepressants. Contramal may interact with these medicines and you may develop serotonin syndrome (see section 4 "Possible side effects").
• coumarin anticoagulants (blood-thinning medicines), such as warfarin, together with Contramal. 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).

Contramal with food and alcohol
Do not drink alcohol during treatment with Contramal, as its effect may be enhanced.
Food intake does not affect the effect of Contramal.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you 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 Contramal capsules.
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 Contramal more than once during breastfeeding; alternatively, if you take Contramal more than once, you must stop breastfeeding.
There is limited data on the effects of Contramal on fertility.
Driving and using machines
Contramal 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 tools requiring a secure footing.
Contramal capsules contain less than 1 mmol (23 mg) of sodium, i.e. essentially “sodium-free”

3. How to take CONTRAMAL

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 Contramal, 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 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 Contramal 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 and adolescents
Contramal 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
Patients with severe hepatic and/or renal impairment must not take Contramal. In cases of mild or moderate impairment, your doctor may advise you to increase the interval between doses.
How and when to take Contramal
Contramal 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 in the evening. You may take the capsules either with or without food.
How long to take Contramal
Do not take Contramal longer than necessary. If long-term treatment is required, your doctor will schedule regular and frequent check-ups (and, if necessary, temporary interruptions of therapy) to determine whether you should continue treatment and at what dose.
If you feel that the analgesic effect of Contramal is too strong or too weak, consult your doctor or pharmacist.
If you take more Contramal than you should
Taking an extra dose by mistake should not cause harmful effects. You may continue taking the medicine as prescribed.
However, 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 Contramal
If you forget to take Contramal, 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 Contramal
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 when and how to stop. This may involve gradually reducing the dose to minimize the risk of developing unnecessary side effects (withdrawal symptoms).
Generally, stopping treatment with Contramal does not lead to withdrawal effects.
However, in rare cases, some people who have taken Contramal for a prolonged period may feel unwell when stopping 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 Contramal, 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 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, rapid 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, shortness of breath, skin swelling) and shock (circulatory failure)
• slow heartbeat
• increase in blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, slow breathing, epileptic seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• epileptic seizures have occurred especially 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 Contramal, 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 decreased or suppressed, sometimes increased), and reduced cognitive and sensory perception (changes in senses and emotional recognition ability, which may lead to judgment errors)
• drug dependence. When treatment is stopped abruptly, withdrawal symptoms may occur (see "If you stop taking Contramal")
• 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 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

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

• decrease in blood sugar levels
• hiccups
• 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 Contramal").

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

5. How to store CONTRAMAL

Keep this medicine 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 individuals for whom it has not been prescribed.
Store below 30°C.
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.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Contramal contains
The active substance is tramadol hydrochloride.
Each capsule contains 50 mg of tramadol hydrochloride.
The other components are: microcrystalline cellulose, sodium carboxymethylstarch (type A), anhydrous colloidal silica, magnesium stearate; the empty capsule shell contains gelatin, yellow iron oxide (E172), titanium dioxide (E171).

Description of the appearance of Contramal 50 mg hard capsules and package contents
Hard capsules, glossy, oblong, yellow in colour.
Pack size: 20 hard capsules.

Marketing Authorization Holder
GRÜNENTHAL ITALIA S.r.l. –
Via Vittor Pisani 16 - 20124 Milan, Italy

Responsible manufacturer for batch release
FARMACEUTICI FORMENTI S.p.A. – Via Di Vittorio, 2 – 21040 Origgio (VA), Italy
GRÜNENTHAL GmbH - Zieglerstraße 6, 52078 Aachen, Germany

Patient Information Leaflet

CONTRAMAL 50 mg/1 ml injectable solution, 100 mg/2 ml injectable solution

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

1. What CONTRAMAL is and what it is used for

Tramadol – the active substance in CONTRAMAL injectable solution – is an analgesic (for pain) belonging to the opioid class, acting on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
CONTRAMAL 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 should know before taking CONTRAMAL

Do not use Contramal

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6)
• in acute alcohol intoxication, sedatives, painkillers or other psychotropic medicines (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 treatment with Contramal (see "Other medicines and Contramal")
• if you have epilepsy and your seizures are not adequately controlled by therapy
• as a substitute in drug detoxification therapy.

Warnings and precautions
Talk to your doctor or pharmacist before taking Contramal if:

• you suffer from disturbances of consciousness (if you feel faint)
• you are in a state of shock (cold sweats may be a sign)
• you have increased intracranial pressure (possible after head trauma or brain diseases)
• you have breathing difficulties
• you have a tendency to epilepsy or seizures, as the risk of an attack may increase
• you suffer from liver or kidney disease
• you suffer from depression and are taking antidepressants, because some of them may interact with tramadol (see "Other medicines and Contramal"). There is a risk, albeit small, 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 syndrome (see section 4 "Possible side effects").

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 Contramal 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 Contramal may increase 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 Contramal, 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 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 Contramal").
For athletes: using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.
Sleep-related breathing disorders
Contramal contains an active ingredient belonging to the opioid group. Opioids may cause sleep-related breathing disorders, such as central sleep apnea (shallow breathing or breathing pauses during sleep) and sleep-related hypoxemia (low blood oxygen levels).
The risk of central sleep apnea depends on the opioid dose. Your doctor may consider reducing the total opioid dose if central sleep apnea occurs.
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.
Contramal may lead to physical and psychological dependence. When Contramal is administered for long periods, its effect may decrease, requiring higher doses (development of tolerance). In patients with a tendency to medicine abuse or who are dependent on medicines, Contramal 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.
Contact your doctor if you experience any of the following symptoms while taking CONTRAMAL:
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.
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 Contramal
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Contramal must not be taken together with MAO inhibitors (certain medicines used for depression).
The intensity and duration of the analgesic effect of Contramal may be reduced if you are taking medicines containing

• carbamazepine (for epileptic seizures)
• ondansetron (to prevent nausea). Your doctor will inform you whether and which doses of Contramal 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 Contramal. You may feel drowsy or weak. In such cases, consult your doctor.
• concomitant use of Contramal and sedatives or sleeping medicines (e.g., benzodiazepines), which 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 Contramal 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 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 Contramal at the same time. Your doctor will tell you whether Contramal is suitable for you.
• certain antidepressants. Contramal 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 Contramal. 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).

Contramal with food, drinks and alcohol
Do not drink alcohol during treatment with Contramal, as its effect may be enhanced.
Food intake does not affect the action of Contramal.
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 regarding the safety of tramadol in pregnant women. Therefore, if you are pregnant, you must not use Contramal injection solution.
Chronic use during pregnancy may lead to withdrawal symptoms in newborns.
Breastfeeding
Tramadol is excreted in breast milk. For this reason, you must not take Contramal more than once during breastfeeding, or alternatively, if you take Contramal more than once, you must stop breastfeeding.
There is limited data on the effects of Contramal on fertility.
Driving and using machines
Contramal may cause drowsiness, dizziness and vision problems (blurred vision). If you feel your reaction ability is impaired, do not drive vehicles or operate machinery, or use tools requiring secure handling.
Contramal injection solution contains less than 1 mmol of sodium (23 mg) per ml, i.e., essentially "sodium-free".

3. How to use CONTRAMAL

Use this medicine exactly as directed by your doctor. If you have any doubts, you must
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 Contramal, 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 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 dosage of up to 8 ml of Contramal 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 dosage 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. Use the lowest dose that provides pain relief. 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 individuals (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 Contramal. In cases of mild or moderate impairment, your doctor may advise you to increase the interval between doses.

How and when to administer Contramal injectable solution
Contramal injectable solution should be injected slowly into a vein (usually in the arm) or into the muscle (typically in the buttock) or subcutaneously. Contramal injectable solution may be diluted in a suitable infusion solution and administered intravenously.

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

Instructions for use
Contramal injectable solution is supplied in breakable ampoules. The ampoule has a scored break line for opening:

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

How long should you take Contramal
Do not use Contramal longer than necessary. If long-term treatment is required, your doctor will schedule regular and frequent check-ups (and may temporarily interrupt treatment if needed) to determine whether you should continue treatment and at what dosage.
If you feel that the analgesic effect of Contramal is too strong or too weak, consult your doctor or pharmacist.

If you take more Contramal than you should
If you have accidentally received an extra dose, this should not cause harmful 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, contact your doctor immediately.

If you forget to take Contramal
If Contramal injectable solution has not been administered, pain may return. Do not administer a double dose to make up for the missed dose; continue treatment as directed.

If you stop taking Contramal
If you stop or discontinue treatment too early, 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 discontinue the medicine, especially after prolonged use, discuss it with your doctor first. Your doctor will advise you when and how to stop, possibly by gradually reducing the dose to minimize the risk of developing unnecessary adverse effects (withdrawal symptoms).
Generally, discontinuation of Contramal does not cause withdrawal effects.
However, in rare cases, some individuals who have taken Contramal for a prolonged period may feel unwell when stopping abruptly.
Specifically, 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 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 Contramal, 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 (urticaria)
• 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 occur particularly 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 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, slow breathing, 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 cause seizures
• changes in appetite
• hallucinations, confusion, sleep disturbances, delirium, anxiety and nightmares
• psychological symptoms may occur after treatment with Contramal, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as mood changes (mainly elevated 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 judgment errors)
• drug dependence. When treatment is stopped abruptly, withdrawal symptoms may occur (see section “If you stop treatment with Contramal”)
• 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

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

• decrease in blood sugar levels
• hiccups
• 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 Contramal”).

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

5. How to store CONTRAMAL

Keep this medicine 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 label. 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 you no longer use. This will help protect the environment.

6. Package contents and other information

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

Description of the appearance of Contramal injectable solution and package contents
Colourless, clear solution.
Contramal injectable solution is contained in transparent glass ampoules, in packages containing 5 ampoules.

Marketing Authorisation Holder
GRÜNENTHAL ITALIA S.r.l. –
Via Vittor Pisani 16 - 20124 Milano

Responsible manufacturer for batch release
FARMACEUTICI FORMENTI S.p.A. – Via di Vittorio, 2 – 21040 Origgio (VA)
GRÜNENTHAL GmbH - Zieglerstraße 6, 52078 Aachen (Germany)

Patient Information Leaflet

CONTRAMAL 100 mg/ml oral drops, solution with dropper

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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist.

Contents of this leaflet

1. What CONTRAMAL is and what it is used for
2. What you need to know before using CONTRAMAL
3. How to use CONTRAMAL
4. Possible adverse reactions
5. How to store CONTRAMAL
6. Package contents and other information

1. What CONTRAMAL is and what it is used for

Tramadol – the active substance in Contramal – is an analgesic (pain reliever) belonging to the opioid class, acting on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Contramal 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 should know before taking CONTRAMAL

Do not take Contramal oral solution with dropper:

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6)
• in acute alcohol, sleeping pills, painkillers or other psychotropic drug poisoning (medicines acting on 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 treatment with Contramal (see “Other medicines and Contramal”)
• if you have epilepsy and your seizures are not adequately controlled by treatment
• as a substitute in drug detoxification therapy.

Warnings and precautions
Talk to your doctor or pharmacist before taking Contramal if:

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

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 Contramal 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 physical or psychological dependence on Contramal 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 Contramal, 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 Contramal”).
For athletes: using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.
Sleep-related breathing disorders
Contramal contains an active ingredient belonging to the opioid group. Opioids may cause sleep-related breathing disorders, such as central sleep apnea (shallow breathing or breathing pauses during sleep) and sleep-related hypoxemia (low blood oxygen levels).
The risk of central sleep apnea depends on the opioid dose. Your doctor may consider reducing the total opioid dosage if central sleep apnea occurs.
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 limit dose of 400 mg.
Contramal may lead to physical and psychological dependence. When Contramal is administered for a long period, its effect may decrease, thus requiring higher doses (development of tolerance). In patients with a tendency to medicine abuse or who are dependent on medicines, Contramal 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 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.
Contact your doctor if you experience any of the following symptoms while taking CONTRAMAL:
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 you need hormonal replacement therapy.
Other medicines and Contramal
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Contramal must not be taken together with MAO inhibitors (some medicines used for depression).
The intensity and duration of the analgesic effect of Contramal may be reduced if you are taking medicines containing:

• carbamazepine (for epileptic seizures)
• ondansetron (to prevent nausea). Your doctor will inform you whether and what dosage of Contramal 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 Contramal. You may feel drowsy or weak. In such cases, consult your doctor.
• Concomitant use of Contramal 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 Contramal 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 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 Contramal at the same time. Your doctor will tell you whether Contramal is suitable for you.
• certain antidepressants; Contramal may interact with these medicines and you may develop serotonin syndrome (see section 4 “Possible side effects”).
• coumarin anticoagulants (blood-thinning medicines), such as warfarin, together with Contramal. The effect of these medicines on blood clotting may be affected, leading to bleeding.
• gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

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.
Contramal with food, drinks and alcohol
Do not drink alcohol during treatment with Contramal, as its effect may be enhanced.
Food intake does not affect the action of Contramal.
Pregnancy, breastfeeding and fertility
If you are pregnant, think 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 take Contramal oral 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 Contramal more than once during breastfeeding; alternatively, if you take Contramal more than once, you should stop breastfeeding.
There is limited data on the effects of Contramal on fertility.
Driving and using machines
Contramal may cause drowsiness, dizziness and vision problems (blurred vision). If you feel your reaction ability is impaired, do not drive vehicles or operate machinery, or use tools requiring stable support.
Contramal 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 Contramal 100 mg/ml oral solution with dropper contains sucrose.
If Contramal oral solution with dropper is used chronically (e.g. for two weeks or longer), it may be harmful to teeth.
Contramal 100 mg/ml oral solution contains macrogol glycerol hydroxystearate, a castor oil derivative that may cause gastrointestinal disturbances and diarrhoea.
Contramal 100 mg/ml oral solution contains 150 mg of propylene glycol per ml.
Contramal 100 mg/ml oral solution contains less than 1 mmol (23 mg) of sodium per ml, i.e. essentially “sodium-free”.

3. How to use CONTRAMAL

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 you can expect from using Contramal, 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 determined based on 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 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. In the absence of specific medical instructions, 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 dosing information based on
body weight, refer to the notes at the end of this leaflet.
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.
For use in children, Contramal oral solution drops with dropper is recommended instead of the
Contramal 30 ml oral solution with dispenser, to allow precise dosing according to the child's body weight.
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 interval between doses.
Patients with severe hepatic or renal impairment / dialysis
Contramal must not be used in 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 Contramal
Take Contramal 100 mg/ml oral solution drops with dropper mixed with sugar or a small amount of
liquid.
For instructions on how to use the dropper, refer to the information at the end of this leaflet.
Food intake does not affect the action of Contramal.
How long should you take Contramal
Do not take Contramal longer than necessary. If long-term treatment is required, your doctor will
monitor you at regular, short 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 Contramal is too strong or too weak, consult your doctor
or pharmacist.
If you take more Contramal 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 Contramal
If you forget to take the oral solution, your pain may return. Do not double the dose to make up for the
missed dose; simply continue taking the medicine as previously directed.
If you stop taking Contramal
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 after long-term use, discuss this first with your doctor. Your doctor will advise you
on when and how to discontinue it, which may involve gradually reducing the dose to minimize the risk of
unnecessary adverse effects (withdrawal symptoms).
Generally, discontinuation symptoms do not occur when stopping treatment with Contramal.
However, in rare cases, some individuals who have taken Contramal for a prolonged period may feel unwell
after abruptly stopping the medicine.
They may:

• feel restless, 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 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 Contramal treatment, consult your doctor.

If you experience any of these symptoms after stopping Contramal, 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 everybody will get 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 occur particularly 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
• increased blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, slow breathing, epileptic seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• epileptic seizures have occurred especially 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 Contramal, varying in nature and intensity depending on the patient's personality and duration of therapy. These may present as mood changes (mainly elevated 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 abruptly discontinued, withdrawal symptoms may occur (see “If you stop taking Contramal”)
• 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, although 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

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

• decrease in blood sugar levels
• hiccups
• 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 should know before taking Contramal”).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at the following address:
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 CONTRAMAL

Keep this medicine 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 that month. This medicine does not require any special storage conditions.
The medicine should be used within 12 months after the first opening of the bottle; after this period, any remaining medicine must be disposed of.
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. Package contents and other information

What Contramal 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 ingredients 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. See the end of section 2 for information on sucrose and macrogol glycerol hydroxystearate.

Description of the appearance of Contramal and package contents
Contramal 100 mg/ml oral drops solution is clear, slightly viscous, and pale yellow in color.
The solution is contained in an amber glass bottle and contains 10 ml of solution.

Marketing Authorization Holder
GRÜNENTHAL ITALIA S.r.l. –
Via Vittor Pisani 16 - 20124 Milano
Responsible manufacturer for batch release
FARMACEUTICI FORMENTI S.p.A. – Via Di Vittorio, 2 – 21040 Origgio (VA)
GRÜNENTHAL GmbH - Zieglerstraße 6, 52078 Aachen (Germany)

Instructions for use of Contramal 100 mg/ml oral drops solution
The Contramal bottle is supplied in a tamper-evident package. The carton is sealed, and the bottle has a security ring. Only when 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 on content quantity
Due to differences in wall and base thickness of the bottle, the liquid level may vary by a few millimeters in the sealed packaging of Contramal 100 mg/ml oral drops solution.

The bottle of Contramal 100 mg/ml oral drops solution comes with a dropper and a child-resistant closure. To open, press down firmly 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 USE CONTRAMAL”.

Content of tramadol hydrochloride in the drops:

Note on dosing of Contramal oral drops solution in children over 1 year of age
Dosing table according to body weight in children (see also HOW TO USE
CONTRAMAL 0.1 mg/ml oral drops solution with dropper)

Package leaflet: information for the patient

CONTRAMAL 100 mg/ml oral solution with dispenser

Tramadol hydrochloride
30 ml bottle
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 could 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 CONTRAMAL is and what it is used for
2. What you need to know before taking CONTRAMAL
3. How to take CONTRAMAL
4. Possible side effects
5. How to store CONTRAMAL
6. Package contents and other information

1. What CONTRAMAL is and what it is used for

Tramadol – the active substance in Contramal – is an analgesic (painkiller) belonging to the opioid class, acting on the central nervous system. It reduces pain by acting on specific nerve cells in the spinal cord and brain.
Contramal 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 should know before taking CONTRAMAL

Do not take Contramal

• if you are allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6)
• in acute alcohol, hypnotic, opioid or other psychotropic drug poisoning (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 before starting treatment with Contramal (see "Other medicines and Contramal")
• if you have epilepsy and your seizures are not adequately controlled by therapy
• as a substitute in drug detoxification therapy.

Warnings and precautions
Talk to your doctor or pharmacist before taking Contramal if:

• you suffer from disturbances of consciousness (if you feel faint)
• you are in a state of shock (cold sweats may be a sign)
• you have increased intracranial pressure (possible after head trauma or brain diseases)
• you have breathing difficulties
• you have a tendency to epilepsy or seizures, as the risk of an attack may increase
• you suffer from liver or kidney disease
• you suffer from depression and are taking antidepressants, because some of them may interact with tramadol (see "Other medicines and Contramal"). 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 syndrome (see section 4 "Possible side effects").

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 Contramal 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 Contramal 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 Contramal, you may have developed physical or psychological dependence:

• You need to take the medicine for a longer period 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 and how to safely discontinue treatment (see section 3, "If you stop taking Contramal").
For athletes: using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Sleep-related breathing disorders
Contramal contains an active substance belonging to the opioid group. Opioids may cause sleep-related breathing disorders, such as central sleep apnea (shallow breathing or breathing pauses during sleep) and sleep-related hypoxemia (low blood oxygen levels).
The risk of central sleep apnea depends on the opioid dose. Your doctor may consider reducing the total opioid dose if central sleep apnea occurs.
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.
Contramal may lead to physical and psychological dependence. When Contramal is administered for a long period, its effect may decrease, requiring higher doses (development of tolerance). In patients with a tendency to medicine abuse or who are dependent on medicines, Contramal 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 of this enzyme, which may lead to different effects in them. Some people may not achieve 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.
Contact your doctor if you experience any of the following symptoms while taking CONTRAMAL:
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.

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

• carbamazepine (for epileptic seizures)
• ondansetron (to prevent nausea). Your doctor will inform you whether and which doses of Contramal 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 Contramal. You may feel drowsy or faint. In such cases, consult your doctor
• Concomitant use of Contramal 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 Contramal 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 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 Contramal at the same time. Your doctor will tell you whether Contramal is suitable for you
• certain antidepressants; Contramal 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 Contramal. The effect of these medicines on blood clotting may be affected, leading to bleeding
• gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

Contramal with food, drinks and alcohol
Do not drink alcohol during treatment with Contramal, as its effect may be enhanced.
Taking food does not affect the effect of Contramal.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect 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 take Contramal 100 mg/ml oral solution with dispenser.
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 Contramal more than once during breastfeeding, or alternatively, if you take Contramal more than once, you must stop breastfeeding.
There is limited data on the effects of Contramal on fertility.

Driving and using machines
Contramal 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 tools that require a secure grip.

Contramal 100 mg/ml oral solution with dispenser 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. This is because Contramal 100 mg/ml oral solution with dispenser contains sucrose. If Contramal oral solution with dispenser is used chronically (e.g., for two weeks or longer), it may be harmful to teeth.
Contramal 100 mg/ml oral solution with dispenser contains macrogol glycerol hydroxystearate, a castor oil derivative that may cause gastrointestinal disturbances and diarrhea.
Contramal 100 mg/ml oral solution contains 150 mg of propylene glycol per ml.
Contramal 100 mg/ml oral solution contains less than 1 mmol (23 mg) of sodium per ml, i.e., essentially "sodium-free".

3. How to take CONTRAMAL

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 Contramal, 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 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 32 sprays per day (e.g., 8 doses of 4 sprays, equivalent to 400 mg of tramadol hydrochloride), 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:
From 4 to 8 sprays (equivalent to 50 or 100 mg of tramadol hydrochloride) every 4–6 hours.
Use in children and adolescents
In children over one year of age, the single dose is 1–2 mg per kg of body weight (1–2 mg of tramadol hydrochloride per kg). For detailed dosing information related to body weight, please read the notes at the end of this leaflet.
In general, the lowest dose capable of relieving pain should be used.
The lowest effective dose that relieves pain should be taken. Daily doses must not exceed 8 mg of tramadol hydrochloride per kg of body weight or 400 mg of tramadol hydrochloride, whichever is lower.
For children, use of the Contramal oral drops solution with dropper is recommended instead of Contramal oral solution with spray dispenser, to allow more accurate dosing according to body weight.
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 interval between doses.
Patients with severe hepatic or renal impairment / dialysis
Patients with severe hepatic and/or renal impairment must not take Contramal. In cases of mild or moderate impairment, your doctor may advise you to increase the interval between doses.
How and when to take Contramal
Take Contramal 100 mg/ml oral solution with spray dispenser with some sugar or a small amount of liquid.
For detailed instructions on the use of the spray dispenser, please read the notes at the end of this leaflet.
How long to take Contramal
Do not take Contramal 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 Contramal is too strong or too weak, consult your doctor or pharmacist.
If you take more Contramal 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 Contramal
If you forget to take Contramal, your pain may return. Do not double the dose to make up for a missed dose. Simply continue taking the oral solution as before.
If you stop taking Contramal
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 with your doctor first. 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 of Contramal does not lead to withdrawal effects.
However, in rare cases, some people who have taken Contramal for a prolonged period may feel unwell when stopping abruptly. 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, 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 Contramal, 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 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 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 who are standing up or undergoing physical exertion
• feeling the need to vomit (nausea), stomach ache (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, swelling of the skin) and shock (circulatory failure)
• slow heartbeat
• increased blood pressure
• abnormal sensations (e.g. tingling, itching, numbness), tremor, slow breathing, epileptic seizures, muscle spasms, uncoordinated movements, temporary loss of consciousness (syncope), speech disorders
• epileptic seizures have occurred especially 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 Contramal, 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 abruptly stopped, withdrawal symptoms may occur (see “If you stop taking Contramal”)
• vision problems, excessive dilation of the pupils (mydriasis), constriction of the pupils (miosis)
• slow breathing, shortness of breath (dyspnoea). If doses above the recommended levels are taken, 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

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

• decrease in blood sugar levels
• hiccups
• 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 Contramal”).

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 the following website:
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 CONTRAMAL

Keep this medicine 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. The expiry date refers to the last day of that 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 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 Contramal contains
The active substance is tramadol hydrochloride.
Each ml of solution contains 100 mg of tramadol hydrochloride (the bottle is equipped with a dispenser; each
administration contains 5 drops and corresponds to 12.5 mg of tramadol).
The other components are: sucrose (solution 0.2 g/ml), propylene glycol, glycerol, sodium cyclamate, sodium saccharin, potassium sorbate, macrogol glycerol hydroxystearate, peppermint flavour, anise flavour, purified water. See the end of section 2 for information on sucrose and macrogol glycerol hydroxystearate.
Description of the appearance of Contramal and contents of the pack
Contramal 100 mg/ml oral solution with dispenser is a clear, slightly viscous solution, tending towards light yellow. The solution is contained in a 30 ml glass bottle.
Marketing Authorization Holder
GRÜNENTHAL ITALIA S.r.l. –
Via Vittor Pisani 16 - 20124 Milan
Responsible manufacturer for batch release
FARMACEUTICI FORMENTI S.p.A. – Via Di Vittorio, 2 – 21040 Origgio (VA)
GRÜNENTHAL GmbH - Zieglerstraße 6, 52078 Aachen (Germany)
Instructions for use of Contramal 100 mg/ml oral solution with dispenser
Note on the quantity of the contents
Due to differences in the thickness of the walls and bottom of the bottle, the liquid level may vary by a few millimeters in the sealed packaging of Contramal 100 mg/ml oral solution with dispenser.
Note on use.

When using the bottle for the first time: press the dispenser a few times until the solution appears (for technical reasons, it is necessary to prime the pump mechanism to ensure regular dispensing).
Place a spoon or glass under the nozzle and press the dispenser. One complete administration delivers an amount equivalent to 5 drops and contains 12.5 mg of tramadol hydrochloride (for dosing instructions, see section 3 - How to take CONTRAMAL 100 mg/ml oral solution with dispenser).
Contramal is available either in a 30 ml bottle with dispenser or in a 10 ml bottle with dropper.
Please note that 1 press of the dispenser (30 ml bottle with dispenser) does not correspond to 1 drop delivered by the dropper (10 ml bottle with dropper). See the table below for further details. Contramal is dispensed by pressing the top part of the dispenser:

Patient information leaflet

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

Tramadol hydrochloride
Read this leaflet carefully before taking this medicine because it contains
important information.

• 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. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist (see section 4).

Contents of this leaflet

1. What CONTRAMAL prolonged-release tablets are and what they are used for.
2. What you need to know before taking CONTRAMAL prolonged-release tablets.
3. How to use CONTRAMAL prolonged-release tablets.
4. Possible side effects.
5. How to store CONTRAMAL prolonged-release tablets.
6. Contents of the pack and other information.

1. What CONTRAMAL is and what it is used for

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

2. What you should know before taking CONTRAMAL prolonged-release tablets.

Do not use Contramal

• if you are allergic to tramadol or any of the excipients of Contramal
• in acute alcohol intoxication, or intoxication with sleeping medicines, painkillers, or other psychotropic medicines (medicines acting on 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 Contramal (see “Other medicines and Contramal”)
• if you have epilepsy and your seizures are not adequately controlled by treatment
• as a substitute in drug detoxification therapy.

Warnings and precautions
Consult your doctor or pharmacist before taking Contramal if

• you suffer from disturbances of consciousness (if you feel faint)
• you are in a state of shock (cold sweats may be a sign)
• you have increased pressure in the brain (possible after head trauma or brain diseases)
• you have breathing difficulties
• you have a tendency to epilepsy or seizures, as the risk of an attack may increase
• you suffer from liver or kidney disease
• you suffer from depression and are taking antidepressants, because some of them may interact with tramadol (see “Other medicines and Contramal”). 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 syndrome (see section 4 “Possible side effects”).

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 Contramal 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.
If you develop physical or psychological dependence, you may feel unable to control the amount of medicine you need or how often you must take it.
The risk of developing physical or psychological dependence varies from person to person. The risk of developing physical or psychological dependence on Contramal 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 Contramal, you may have developed physical or psychological dependence:

• You need to take the medicine for a longer period 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 stop treatment and how to do so safely (see section 3, “If you stop taking Contramal”).
For athletes: using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Sleep-related breathing disorders
Contramal contains an active substance belonging to the opioid group. Opioids may cause sleep-related breathing disorders, such as central sleep apnea (shallow breathing or breathing pauses during sleep) and sleep-related hypoxemia (low blood oxygen levels).
The risk of central sleep apnea depends on the opioid dose. Your doctor may consider reducing the total opioid dose if central sleep apnea occurs.
Seizures have been reported in patients taking tramadol at recommended doses. The risk may increase when tramadol doses exceed the recommended amounts, beyond the maximum dose (400 mg).
Contramal may lead to physical and psychological dependence. When Contramal is administered for a long period, its effect may decrease, requiring higher doses (development of tolerance).
In patients with a tendency to abuse medicines or who are dependent on medicines, Contramal 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 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.
Contact your doctor if you experience any of the following symptoms while taking Contramal: 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 you need hormone replacement therapy.

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

• carbamazepine (for epileptic seizures)
• ondansetron (to prevent nausea). Your doctor will inform you whether and which doses of Contramal 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 Contramal. You may feel drowsy or weak. If this occurs, inform your doctor.
• The concomitant use of Contramal and sedative medicines 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 possible. However, if your doctor prescribes Contramal 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 carefully follow the dosing recommendations provided by your doctor. 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 (epileptic fits), such as certain antidepressants or antipsychotics. The risk of seizures may increase if you are taking these medicines together with Contramal. Your doctor will advise you whether Contramal is suitable for you.
• certain antidepressants; Contramal may interact with these medicines and you may develop serotonin syndrome (see section 4 “Possible side effects”).
• coumarin anticoagulants (blood-thinning medicines), such as warfarin, together with Contramal. The effect of these medicines on blood clotting may be affected, leading to bleeding.
• gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

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

Pregnancy, breastfeeding, and fertility
If you are pregnant, think 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 Contramal.
Chronic use during pregnancy may lead to withdrawal symptoms in newborns.
Breastfeeding
Tramadol is excreted in breast milk. Therefore, you should not take Contramal more than once during breastfeeding, or alternatively, if you take Contramal more than once, you should stop breastfeeding.
Clinical experience in humans suggests that tramadol does not affect male or female fertility.

Driving and using machines
Contramal may cause drowsiness, dizziness, and vision problems (blurred vision), and may therefore impair your reactions. If you feel that your ability to react is affected, do not drive vehicles or operate machinery, and do not use electrical tools or equipment.

Contramal contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine, which contains lactose.

3. How to use CONTRAMAL

Always 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 you can expect from using Contramal, 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 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 400 mg 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 prolonged-release tablet of Contramal 150 mg twice daily (equivalent to 300 mg of tramadol
hydrochloride per day), preferably in the morning and evening.
One prolonged-release tablet of Contramal 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 Contramal.
If needed, the dose may be increased up to 150 mg or 200 mg twice daily (equivalent to 300 – 400 mg
of tramadol hydrochloride per day).
Do not take more than 400 mg of tramadol hydrochloride per day, unless otherwise prescribed by your
doctor.
Children
Contramal prolonged-release tablets are not suitable for children under 12 years of age.
Elderly
In elderly patients (over 75 years of age), elimination of tramadol may be slower. 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 Contramal. In case of mild or
moderate impairment, your doctor may advise you to increase the interval between doses.
How and when to take Contramal
Contramal prolonged-release tablets should be taken orally.
Always swallow Contramal 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 Contramal
Do not take Contramal longer than necessary. If long-term treatment is required, your doctor will
monitor you at regular and 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 Contramal is too strong or too weak, consult your doctor or
pharmacist.
If you take more Contramal 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 Contramal
If you forget to take the tablets, your pain may return. Do not double the dose to make up for the
missed dose; simply continue taking the tablets as previously scheduled.
If you stop taking Contramal
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 when and how to stop. This may involve gradually reducing the dose to reduce
the likelihood of developing unnecessary adverse effects (withdrawal symptoms).
Generally, discontinuation of Contramal does not lead to withdrawal effects.
However, in rare cases, some people may feel unwell when abruptly stopping Contramal prolonged-release
tablets after prolonged use. You may feel restless, anxious, nervous, or weak. You may become
hyperactive, have difficulty sleeping, or experience gastrointestinal disturbances. Very few people may
experience panic attacks, hallucinations, unusual sensations such as itching, tingling, numbness, or
ringing in the ears (tinnitus). In addition, very rarely, unusual CNS symptoms such as confusion,
delusion, altered perception of one's own personality (depersonalization), altered perception of reality
(derealization), and feelings of persecution (paranoia) have been reported. If you experience any of these
symptoms after stopping treatment with Contramal, consult your doctor.
If you have any questions about the use of this medicine, please contact your doctor or pharmacist.

4. Possible side effects

Like all medicines, Contramal 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 and/or difficulty swallowing or hives together with difficulty
breathing.

The most common side effects during treatment with Contramal are nausea and dizziness, occurring in
more than 1 out of 10 people.

Very common: may affect more than 1 in 10 people

• dizziness
• nausea

Common: may affect up to 1 in 10 people

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

Uncommon: may affect up to 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
• vomiting urges, stomach discomfort (feeling of heaviness, bloating), diarrhoea
• skin reactions (e.g. itching, rash)

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

• allergic reactions (e.g. difficulty breathing, wheezing, skin swelling) and shock (sudden drop in blood pressure)
• slow heartbeat
• increase in blood pressure
• unusual sensations (itching, tingling, numbness), tremors, slowed breathing, epileptic seizures, muscle spasms, uncoordinated movements, transient loss of consciousness (syncope), speech disturbances
• epileptic seizures have occurred mainly after administration of high doses of tramadol or concomitant treatment with medicines that predispose to seizures
• changes in appetite
• hallucinations, confusion, sleep disturbances, delirium, anxiety and nightmares
• psychological disturbances may occur after treatment with Contramal. Their intensity and nature may vary (depending on the patient's personality and duration of therapy). They may present as changes in mood (usually euphoria, rarely irritability), activity (usually reduced, rarely increased), and reduced sensory and cognitive perception (alterations in sensations and ability to discriminate, which may lead to misjudgements)
• dependence may occur
• blurred vision, excessive dilation of the pupils (mydriasis), constriction of the pupil (miosis)
• slowed breathing, shortness of breath (dyspnoea)
• worsening of bronchial asthma has been observed; however, it has not been established whether this could have been caused by tramadol. If recommended doses are exceeded, or if other medicines that depress brain function are taken concomitantly, breathing may slow down
• muscle weakness
• difficulty or pain when urinating, reduced urine output (dysuria)

Very rare: may affect up to 1 in 10,000 people

• increased levels of liver enzymes

Not known: frequency cannot be estimated from the available data

• decrease in blood sugar levels
• hiccups
• 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 Contramal”).

When treatment is stopped abruptly, withdrawal symptoms may occur (see “If you stop taking Contramal”).

Reporting of side effects
If you experience any side effects, inform 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 CONTRAMAL

Keep this medicine 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 Contramal 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Contramal contains
The active substance is tramadol hydrochloride.
Contramal prolonged-release tablets 150 mg
Each tablet contains 150 mg of tramadol hydrochloride.
The excipients are – core: microcrystalline cellulose, hypromellose 100,000 mPa·s, magnesium stearate, anhydrous colloidal silica; – coating: hypromellose 6 mPa·s, lactose monohydrate, macrogol 6000, propylene glycol, talc, titanium dioxide (E171), quinoline yellow (E104), iron oxide red (E172).
Contramal prolonged-release tablets 200 mg
Each tablet contains 200 mg of tramadol hydrochloride.
The excipients are – core: microcrystalline cellulose, hypromellose 100,000 mPa·s, magnesium stearate, anhydrous colloidal silica; – coating: hypromellose 6 mPa·s, lactose monohydrate, macrogol 6000, propylene glycol, talc, titanium dioxide (E171), quinoline yellow (E104), iron oxide red (E172), iron oxide brown (E172).

Description of the appearance of Contramal and contents of the pack
Contramal 150 mg prolonged-release tablets are round, biconvex, light orange tablets, with the code "T2" engraved on one side and the logo  on the other.
Contramal 200 mg prolonged-release tablets are round, biconvex, dark orange tablets, with the code "T3" engraved on one side and the logo  on the other.
Contramal is packaged in blisters and sold in boxes containing 10 tablets.
Contramal is also available in unit-dose divisible blisters, sold in boxes containing 10x1, 20x1, 30x1, 50x1, 60x1, 100x1, and 150x1 ((10x1)x15) tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder: GRÜNENTHAL ITALIA S.r.l.
Via Carlo Bo 11 – 20143 Milan, Italy
Manufacturer: Grünenthal GmbH
Zieglerstraße 6 - 52078 Aachen, Germany
Farmaceutici Formenti S.p.A.
Via di Vittorio, 2 – 21040 Origgio (VA), Italy

This medicinal product is authorized in other EU countries under the following names:
Belgium: Contramal retard 50 mg, 100 mg, 150 mg, 200 mg
Denmark: Nobligan retard 100 mg, 150 mg, 200 mg
Finland: Tramal retard 50 mg, 100 mg, 150 mg, 200 mg
France: Topalgic L.P. 100 mg, 150 mg, 200 mg
Germany: Tramal retard 50 mg, 100 mg, 150 mg, 200 mg
Italy: Contramal 150 mg, 200 mg
Luxembourg: Contramal retard 50 mg, 100 mg, 150 mg, 200 mg
Netherlands: Tramal retard 100 mg
Poland: Tramal retard 50 mg
Portugal: Tramal retard 100 mg, 150 mg, 200 mg
Slovenia: Tramal 50 mg
Spain: Adolonta retard 50 mg, 100 mg, 150 mg, 200 mg
Sweden: Nobligan retard 100 mg, 200 mg

This leaflet was last approved on: