Tramadol and paracetamol EG

Patient Information Leaflet

Tramadol and Paracetamol EG 37.5 mg/325 mg Film-coated Tablets

Generic Medicine
Please read all of this leaflet carefully before you take this medicine because it contains important information for you.

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

Contents of this leaflet

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

1. What Tramadolo e paracetamolo EG is and what it is used for

Tramadolo e paracetamolo EG contains the active substances tramadol hydrochloride and paracetamol. Tramadol hydrochloride belongs to a group of medicines called opioids and paracetamol belongs to a group of medicines called analgesics.
Tramadolo e paracetamolo EG is used to treat moderate to severe pain. Your doctor will prescribe this medicine to you if he or she considers that a combination of tramadol hydrochloride and paracetamol is appropriate.
Tramadolo e paracetamolo EG should be administered to adults and adolescents over 12 years of age.

2. What you need to know before taking Tramadol and paracetamol EG

Do not take Tramadol and paracetamol EG

• if you are allergic to tramadol, paracetamol, or any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant;
• in acute alcohol intoxication;
• if you are taking medicines for sleep, painkillers acting on the central nervous system, opioids, or medicines affecting mood and emotions;
• if you are currently taking monoamine oxidase inhibitors (MAO inhibitors) for the treatment of depression or Parkinson’s disease, or if you have taken MAO inhibitors within the previous 2 weeks;
• if you suffer from severe liver disease;
• if you have epilepsy and your seizures are not adequately controlled by your current medication;
• if you suffer from severe haemolytic anaemia (a blood disorder characterised by destruction of red blood cells).

Warnings and precautions
Talk to your doctor or pharmacist before taking Tramadol and paracetamol EG:

• if you are already taking medicines containing paracetamol, due to the risk of liver damage;
• if you are already taking medicines containing tramadol;
• if you have severe kidney problems. In this case, use of Tramadol and paracetamol EG is not recommended. In case of moderate kidney problems, the dosing interval should be extended to 12 hours;
• extreme tiredness, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These symptoms may indicate adrenal insufficiency (low cortisol levels). If you experience these symptoms, contact your doctor, who will decide whether hormonal replacement is needed;
• if you have bile duct disorders;
• if you have severe liver problems;
• if you have severe breathing difficulties, such as asthma or serious lung conditions;
• if you are opioid-dependent or have previously abused drugs or suffered from drug dependence (e.g. morphine); treatment with Tramadol and paracetamol EG should be short-term and under medical supervision;
• if you have had head trauma, shock, increased intracranial pressure, altered mental status, or severe headaches associated with vomiting (malaise);
• if you are prone to seizures;
• if you have diabetes, because Tramadol and paracetamol EG may reduce blood sugar levels (hypoglycaemia);
• if you are about to undergo anaesthesia. Inform your doctor or dentist that you are being treated with Tramadol and paracetamol EG;
• if you suffer from depression and are taking antidepressants, as some of them may interact with tramadol (see “Other medicines and Tramadol and paracetamol EG”).

In all the above cases, this medicine should be used only with caution.
There is a small but possible risk that you may develop 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”).

Sleep-related breathing disorders
Tramadol and paracetamol EG may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low blood oxygen levels). Symptoms may include breathing pauses during sleep, night awakenings due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor, who may consider reducing the dose.

Tramadol is metabolised in the liver via an enzyme. Some people have variations in this enzyme, which may affect them differently. In some individuals, pain relief may be insufficient, while others may be more prone to serious side effects. If you notice any of the following side effects, stop taking this medicine and contact your doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, feeling unwell or malaise, constipation, loss of appetite.

Tramadol must not be used as a substitute therapy in patients dependent on opioids, as it does not suppress morphine withdrawal symptoms.

Tramadol may cause seizures even at recommended doses. Therefore, patients with controlled epilepsy or those prone to epileptic/convulsive seizures should only be treated with Tramadol and paracetamol EG if absolutely necessary.

Children
Tramadol and paracetamol EG is not recommended in children under 12 years of age. The efficacy and safety of use have not been established in children.

Use in children with respiratory problems
Tramadol is not recommended in children with respiratory problems, as symptoms of tramadol toxicity may worsen in these children.

Abuse
When taking medicines such as Tramadol and paracetamol EG, tolerance and physical and/or psychological dependence may develop, especially with long-term use. Your doctor will regularly assess whether continued use of pain medication is necessary.

Withdrawal symptoms may occur even at therapeutic doses and during short-term treatment. Withdrawal symptoms can be avoided by gradually reducing the dose, especially if you have been taking Tramadol and paracetamol EG for a long time.

Other medicines and Tramadol and paracetamol EG
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Important: This medicine contains paracetamol and tramadol. Inform your doctor if you are taking any other medicines containing paracetamol or tramadol, so as not to exceed the maximum recommended daily doses.

Tramadol and paracetamol EG must not be taken together with the following medicines:

Monoamine oxidase inhibitors (MAO inhibitors), used to treat depression and Parkinson’s disease, due to the risk of developing serotonin syndrome. Symptoms of serotonin syndrome include: diarrhoea, rapid heartbeat, sweating, tremors, confusion up to coma. If you are taking MAO inhibitors, you must stop treatment at least two weeks before starting Tramadol and paracetamol EG (see section “Do not take Tramadol and paracetamol EG”).

The use of Tramadol and paracetamol EG is not recommended with the following medicines:

• Carbamazepine (a medicine used to treat epilepsy or certain types of pain) and other enzyme inducers. Concomitant use of these medicines may reduce the effectiveness and duration of tramadol’s effect.
• Painkillers (buprenorphine, nalbuphine, pentazocine). Concomitant use of these medicines may reduce the analgesic effect of Tramadol and paracetamol EG and may cause withdrawal symptoms. Tramadol and paracetamol EG may increase the risk of side effects if you are also taking the following medicines:
• Certain antidepressants and triptans used to treat migraine; Tramadol and paracetamol EG may interact with these medicines and may cause serotonin syndrome (see section 4 “Possible side effects”).
• Medicines that may cause seizures (epileptic fits), e.g. certain antidepressants, antipsychotics, or bupropion. The risk of seizure may increase if Tramadol and paracetamol EG is taken concomitantly. Your doctor will inform you whether Tramadol and paracetamol EG is suitable for you.
• Other opioid-like medicines (including cough medicines or opioid replacement therapies), barbiturates, and benzodiazepines (sedatives). Taking these medicines concomitantly may increase the risk of respiratory depression, which can be fatal in case of overdose. Concomitant use of Tramadol and paracetamol EG with sedatives or sleep medicines such as benzodiazepines or related drugs increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and is potentially fatal. Therefore, concomitant use should only be considered when no other therapeutic options are available. If your doctor prescribes Tramadol and paracetamol EG together with sedatives, your doctor will determine the appropriate dose and duration of concomitant treatment.

Inform your doctor about any sedatives you are taking and strictly follow their instructions.
It may be helpful for friends or relatives to be aware of the signs and symptoms listed above. Contact your doctor if any of these symptoms occur.

• Other central nervous system depressants, anxiolytics (used to reduce fear), hypnotics, sedative antidepressants, sedative antihistamines (used to treat allergies), neuroleptics (used to treat psychosis), centrally-acting antihypertensives (used to lower blood pressure), thalidomide (a sedative), and baclofen (a muscle relaxant). These medicines may worsen central depression. The effect on alertness may make driving or operating machinery dangerous.
• Warfarin and warfarin-like medicines (used to thin the blood). The effectiveness of these medicines may be affected. Your doctor may need to monitor your prothrombin time regularly.
• Other medicines known to inhibit the liver enzyme “CYP3A4”, such as ketoconazole (an antifungal medicine) and erythromycin (an antibiotic), as they may affect tramadol’s activity.
• Metoclopramide or domperidone (for treating nausea and vomiting/malaise). The absorption of paracetamol may increase if these medicines are taken concomitantly.
• Colestiramine (for lowering blood cholesterol), as the absorption of Tramadol and paracetamol EG may be reduced.
• Altered effectiveness of Tramadol and paracetamol EG may occur following the use of ondansetron (used to prevent vomiting before and after surgery). Inform your doctor or pharmacist if you are taking:
• Flucloxacillin (an antibiotic), due to a serious risk of blood and fluid abnormalities (metabolic acidosis with high anion gap), which must be treated urgently and may occur particularly in cases of severe renal impairment, sepsis (when bacteria and their toxins circulate in the blood causing organ damage), malnutrition, chronic alcoholism, and when maximum daily doses of paracetamol are used.

Tramadol and paracetamol EG with food, drinks and alcohol
Tramadol and paracetamol EG can be taken regardless of food intake. Do not drink alcohol while taking Tramadol and paracetamol EG, as it may increase the sedative effect of the treatment and make driving or operating machinery dangerous.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
This medicine must not be used during pregnancy.
Long-term treatment during pregnancy may lead to withdrawal symptoms in the newborn due to dependence.

Breastfeeding
Tramadol is excreted in breast milk. For this reason, you must not take Tramadol and paracetamol EG more than once during breastfeeding, or you must stop breastfeeding if you need to take Tramadol and paracetamol EG multiple times.

Effects of Tramadol and paracetamol EG on fertility are unknown. Post-marketing data do not suggest an effect of tramadol on fertility.

Driving and using machines
This medicine may cause drowsiness or dizziness, which may impair your ability to drive or operate machinery safely, especially if you also consume alcohol or are taking sedative medicines.
Do not drive or operate machinery until you know how this medicine affects you.

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

3. How to take Tramadol and paracetamol EG

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Your doctor will prescribe the dosage based on the intensity of your pain. You will be prescribed the lowest effective dose for the shortest possible duration.

Recommended dose:
Adults and adolescents over 12 years of age

• The recommended initial dose is 1 tablet in the morning and 1 tablet in the evening. The interval between doses must not be less than 6 hours.
• If necessary, you may take more tablets per day, but you must not exceed the maximum daily dose of 8 tablets (equivalent to 300 mg of tramadol and 2,600 mg of paracetamol). Do not take other medicines containing paracetamol or tramadol hydrochloride to avoid overdose.

Elderly patients
Elimination of tramadol may be delayed in elderly patients (over 75 years of age). If this applies to you, your doctor may recommend increasing the interval between doses.

Severe liver or kidney disease (insufficiency)/dialysed patients
Patients with severe hepatic and/or renal insufficiency must not take Tramadol and paracetamol EG. In cases of mild to moderate impairment, your doctor may recommend prolonging the interval between doses.

Children
Tramadol and paracetamol EG is not recommended for children under 12 years of age.

Method of administration

• The tablets should be taken orally.
• Swallow the tablets whole with a sufficient amount of liquid (e.g. a 200 ml glass of water). The tablets must not be broken or chewed.

Duration of treatment
Do not take this medicine for longer than strictly necessary (considering the nature and severity of your condition). If repeated or long-term treatment with this medicine is required, careful and regular monitoring must be carried out to assess whether continued therapy is still needed. Whenever possible, long-term treatment should include treatment-free intervals.

If you take more Tramadol and paracetamol EG than you should

• If you have taken more tablets than prescribed, contact your doctor immediately or go to the nearest emergency department.
• Overdose may cause nausea (feeling unwell), miosis (pupil constriction), vomiting, anorexia (loss of appetite), abdominal pain, cardiovascular collapse, disturbances in consciousness including coma, seizures, and respiratory depression which may lead to respiratory arrest.
• Liver damage may become apparent 12–48 hours after ingestion. In cases of severe poisoning, liver failure may progress to severe brain disease (encephalopathy), coma, and death. Acute kidney failure with tubular necrosis (cell destruction) may also occur, even in the absence of severe liver damage. Cardiac arrhythmias (irregular heartbeat) and pancreatitis (inflammation of the pancreas) have also been reported.

If you forget to take Tramadol and paracetamol EG
If you forget to take a dose, you may skip the missed dose and continue your treatment as usual. Alternatively, you may take the missed tablet, provided that you maintain a 6-hour interval before the next dose.
Do not take a double dose to make up for a forgotten tablet.

If you stop taking Tramadol and paracetamol EG
Do not stop treatment with this medicine without first consulting your doctor.
Do not stop taking this medicine suddenly unless instructed by your doctor. If you wish to discontinue treatment, consult your doctor first, especially if you have been taking the medicine for a long time. Your doctor will advise you when and how to stop treatment, which may involve gradually reducing the dose to minimize the risk of developing unnecessary adverse effects (withdrawal symptoms).

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Very common: may affect more than 1 in 10 people

• dizziness, drowsiness;
• nausea.

Common: may affect up to 1 in 10 people

• confusion, mood changes, anxiety, nervousness, euphoria, sleep disorders;
• headache, tremors;
• vomiting (nausea), constipation, dry mouth, diarrhoea, abdominal pain, digestive problems, flatulence;
• excessive sweating, itching.

Uncommon: may affect up to 1 in 100 people

• depression, hallucinations (hearing, seeing or sensing things that are not real), nightmares, memory loss;
• involuntary muscle contractions, tingling or numbness in the limbs (paraesthesiae), ringing in the ears (tinnitus);
• increased blood pressure (hypertension), palpitations, heart rhythm disorders (fast or irregular heartbeat);
• difficulty breathing (dyspnoea);
• difficulty swallowing, blood in the stools;
• increased transaminase levels (a liver enzyme);
• skin reactions (e.g. rashes, urticaria);
• albuminuria (albumin (a protein) in the urine), difficulty urinating (dysuria), urinary retention;
• chills, hot flushes, chest pain.

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

• delirium;
• drug dependence;
• difficulty performing coordinated movements, epileptic seizures (convulsions), speech disorders;
• blurred vision;
• fainting;
• constricted pupils (miosis) or dilated pupils (mydriasis).

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

• excessive use (abuse) of the medicine.

Not known (frequency cannot be estimated from the available data)

• low blood sugar levels (hypoglycaemia).

The following are side effects reported with the individual components.

Tramadol:

• worsening of asthma;
• low blood pressure, slowed heart rate, fainting; mood changes, altered activity, altered behaviour and perception;
• in rare cases, changes in appetite, muscle weakness, slower or weaker breathing, allergic reaction characterised by sudden swelling of the face and neck, breathing difficulties or low blood pressure and fainting. If this happens to you, stop treatment and consult a doctor immediately. You must not restart taking this medicine.
• withdrawal syndrome (anxiety, restlessness, nervousness, insomnia, tremors, gastrointestinal disturbances) after prolonged treatment. Other symptoms, observed very rarely after abrupt discontinuation of tramadol, include: panic attacks, severe anxiety, hallucinations, tingling sensation in the limbs, ringing in the ears.
• cases of SIADH (syndrome of inappropriate antidiuretic hormone secretion) and hyponatraemia (low sodium levels in the blood) have been reported.
• rarely, an increase in prothrombin time following the use of warfarin has been observed.
• frequency not known: hiccups; sleep-related breathing disorders (central sleep apnoea syndrome); serotonin syndrome, which may present as changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2 “What you should know before taking Tramadol and paracetamol EG”).

Paracetamol:

• abnormally low levels of certain blood components (blood dyscrasia), including reduced platelets in the blood (thrombocytopenia) and reduced white blood cells (agranulocytosis); prothrombin deficiency.
• in very rare cases, serious skin reactions have been reported.

Reporting of side effects

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

5. How to store Tramadol and paracetamol EG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and on the carton. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine 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 Tramadol and paracetamol EG contains

• The active substances are: 37.5 mg tramadol hydrochloride and 325 mg paracetamol.
• The other components are: Core of the film-coated tablet:
• Pregelatinized starch
• Corn starch
• Sodium carboxymethyl starch (Type A)
• Microcrystalline cellulose (Avicel PH 102)
• Magnesium stearate
  Film coating:
• Opadry Yellow 03K82345 (Hypromellose 6 cPs (E464), titanium dioxide (E171), triacetin, iron oxide yellow (E172))

Description of the appearance of Tramadol and paracetamol EG and package contents
Light yellow, oblong, biconvex, film-coated tablet, smooth on both sides.
Pack sizes: Blister packs of 20 tablets in opaque white PVC-PVdC/Al or PVC/Al.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
EG S.p.A., Via Pavia 6, 20136 Milan, Italy

Manufacturers
STADA Arzneimittel AG, Stadastrasse 2–18, 61118 Bad Vilbel, Germany
MEDIS INTERNATIONAL a.s., Výrobní závod Bolatice, Prúmyslová 961/16, 747 23 Bolatice, Czech Republic
Meiji Pharma Spain, Avda de Madrid 94, 28802 Alcalá de Henares, Madrid, Spain
MARTIN DOW PHARMACEUTICALS, Goualle Le Puy, Champ de Lachaud, 19250 Meymac, France