TRAMADOL/PARACETAMOL COMBIX 37.5 mg/325 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Tramadol/ParacetamolCombix 37.5 mg/325 mg film-coated tablets EFG

Tramadol hydrochloride/Paracetamol

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Tramadol/Paracetamol Combix and what is it used for

Tramadol/Paracetamol Combix is a combination of two pain relievers, tramadol and paracetamol, which work together to relieve pain.

Tramadol/Paracetamol Combix is indicated for the symptomatic treatment of moderate to severe pain, when your doctor considers that a combination of tramadol and paracetamol is necessary.

Tramadol/Paracetamol Combix should only be used by adults and children over 12 years of age.

2. What you need to know before you take Tramadol/Paracetamol Combix

Do not take Tramadol/Paracetamol Combix

• if you are allergic to tramadol, paracetamol or any of the other ingredients of this medicine (listed in section 6).
• in case of acute alcohol intoxication, if you are taking medicines for the treatment of insomnia, potent analgesics (opioids), or other psychotropic medicines (medicines that can alter mood and emotions).
• if you are taking MAO inhibitors (certain medicines used to treat depression or Parkinson's disease), or if you have taken them in the last 14 days before treatment with Tramadol/Paracetamol Combix.
• if you have severe liver disease.
• if you have uncontrolled epilepsy.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Tramadol/Paracetamol Combix:

• if you are taking other medicines that contain paracetamol or tramadol,
• if you have liver problems or liver disease or if you notice that your eyes or skin turn yellow. This may be a sign of jaundice or problems with your bile ducts,
• if you have kidney problems,
• if you have severe breathing difficulties, for example asthma or severe lung problems,
• if you have epilepsy or have had seizures,
• if you have recently had a head injury, severe headaches associated with vomiting,
• if you have been dependent on any other medicine used for pain relief, for example morphine,
• if you are taking other medicines for pain relief that contain buprenorphine, nalbuphine or pentazocine,
• if you are going to be anaesthetized. Tell your doctor or dentist that you are using Tramadol/Paracetamol Combix.
• if you suffer from depression and are taking antidepressants, as some may interact with tramadol (see "Taking Tramadol/Paracetamol Combix with other medicines").

During treatment with Tramadol/Paracetamol Combix, inform your doctor immediately if:

If you have severe illnesses, such as severe kidney failure or sepsis (when bacteria and their toxins circulate in the blood, causing damage to organs), or if you suffer from malnutrition, chronic alcoholism or if you are also taking flucloxacillin (an antibiotic). A serious disease called metabolic acidosis (an anomaly in the blood and fluids) has been reported in patients in these situations when paracetamol is used at regular doses for a prolonged period or when paracetamol is taken with flucloxacillin. The symptoms of metabolic acidosis may include: severe breathing difficulties with deep and rapid breathing, drowsiness, feeling unwell (nausea) and vomiting.

Tolerance, dependence and addiction

This medicine contains tramadol, which is an opioid medicine. Repeated use of opioids can make the medicine less effective (you get used to it, which is known as tolerance). Repeated use of tramadol/paracetamol can also lead to dependence, abuse and addiction, which can result in a potentially life-threatening overdose. The risk of these side effects may increase with higher doses and longer use.

Dependence or addiction can make you feel that you no longer control the amount of medicine you need to take or how often you need to take it.

The risk of becoming dependent or addicted varies from person to person. You may have a higher risk of becoming dependent or addicted to tramadol/paracetamol if:

• You or someone in your family has abused or been dependent on alcohol, prescription medicines or illegal drugs ("addiction").
• You are a smoker.
• You have ever had problems with your mood (depression, anxiety or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs while taking tramadol/paracetamol, it could be a sign that you have become dependent or addicted:

• You need to take the medicine for longer than advised by your doctor
• You need to take more than the recommended dose
• You use the medicine for reasons other than those prescribed, for example "to calm down" or "to sleep"
• You have repeatedly tried and failed to stop or control the use of the medicine
• When you stop taking the medicine, you feel unwell, and you feel better when you take it again ("withdrawal effect")

If you observe any of these signs, talk to your doctor so that they can indicate the best course of treatment for you, including when it is appropriate to stop taking it and how to do so safely (see section 3, "If you stop taking Tramadol/Paracetamol Combix").

Respiratory disorders related to sleep

Tramadol/Paracetamol Combix may cause sleep-related respiratory disorders, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen level in the blood). Among the symptoms may be pauses in breathing during sleep, nighttime awakenings due to lack of breath, difficulty maintaining sleep or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor. They may consider reducing the dose.

Talk to your doctor or pharmacist if you experience any of the following symptoms while taking Tramadol/Paracetamol Combix:

Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting or low blood pressure. They may be indicators of adrenal insufficiency (low cortisol levels). If you have these symptoms, contact your doctor, who will decide if you need to take hormonal supplements.

If you have or have had any of these problems while taking Tramadol/Paracetamol Combix, please inform your doctor. They will decide if you should continue taking this medicine.

There is a weak risk that you may experience a serotonin syndrome that can occur after taking tramadol in combination with certain antidepressants or tramadol alone. Consult a doctor immediately if you present any of the symptoms related to this serious syndrome (see section 4 "Possible side effects").

Taking Tramadol/Paracetamol Combix with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

• Gabapentin or pregabalin for the treatment of epilepsy or pain due to nerve problems (neuropathic pain).

Important:this medicine contains paracetamol and tramadol. Tell your doctor if you are taking any other medicine that contains paracetamol or tramadol, so that you do not exceed the maximum daily dose.

Do not take Tramadol/Paracetamol Combix with monoamine oxidase inhibitors (MAOIs) (see section "Do not take Tramadol/Paracetamol Combix").

Flucloxacillin (antibiotic), due to a serious risk of alteration of blood and fluids (called metabolic acidosis with high anion gap) that must be treated urgently.

It is contraindicated to use Tramadol/Paracetamol Combix if you are being treated with:

• Carbamazepine (a medicine normally used to treat epilepsy or certain types of pain, such as intense pain attacks in the face called trigeminal neuralgia),
• Buprenorphine, nalbuphine or pentazocine (opioid analgesic). Pain relief may be reduced.

The risk of side effects increases if you also use:

• Triptans (for the treatment of migraine) or selective serotonin reuptake inhibitors, "SSRIs" (for the treatment of depression). If you experience confusion, agitation, fever, sweating, uncoordinated movements of the limbs or eyes, uncontrolled muscle contractions or diarrhea, you should call your doctor.
• Sedatives, sleeping medicines, other analgesics such as morphine and codeine (also when used for the treatment of cough), baclofen (muscle relaxant), some medicines to lower blood pressure, antidepressants or medicines for the treatment of allergies. You may feel drowsy or dizzy. If this happens, consult your doctor.
• Antidepressants, anesthetics, neuroleptics (medicines that affect mood) or bupropion (a medicine used as an aid to quit smoking). The risk of having a seizure may increase. Your doctor will tell you if Tramadol/Paracetamol Combix is suitable for you.
• Warfarin or phenprocoumon (a medicine used to prevent blood clots). The effectiveness of these medicines may be altered, and there is a risk of bleeding. You should inform your doctor immediately of any prolonged or unexpected bleeding.
• If you are taking medicines that can cause seizures, such as certain antidepressants or antipsychotics. The risk of seizures increases if you take Tramadol/Paracetamol Combix at the same time as these medicines. Your doctor will tell you if Tramadol/Paracetamol Combix is suitable for you.
• If you are taking medicines for the treatment of depression. Tramadol/Paracetamol Combix may interact with these medicines, and you may experience a serotonin syndrome (see the section 4 "possible side effects").

The effectiveness of Tramadol/Paracetamol Combix may be altered if you also use:

• Metoclopramide, domperidone or ondansetron (medicines for the treatment of nausea and vomiting),
• Colestyramine (a medicine that reduces cholesterol in the blood),
• Ketoconazole and erythromycin (medicines used against infections).

Your doctor will know which medicines are safe to use with Tramadol/Paracetamol Combix.

Taking Tramadol/Paracetamol Combix with food, drinks and alcohol

Tramadol/Paracetamol Combix may make you feel drowsy. Alcohol may make you feel more drowsy, so it is recommended not to drink alcohol while taking Tramadol/Paracetamol Combix.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Because Tramadol/Paracetamol Combix contains tramadol, it is not recommended to use this medicine during pregnancy. If you become pregnant during treatment with Tramadol/Paracetamol Combix, consult your doctor before taking the next tablet.

Breastfeeding

Tramadol may pass into breast milk. For this reason, you should not take Tramadol/Paracetamol Combix more than once during breastfeeding, or otherwise, if you take Tramadol/Paracetamol Combix more than once, you should stop breastfeeding.

Driving and using machines

Ask your doctor if you can drive or use machines during treatment with Tramadol/Paracetamol Combix. It is important that before driving or using machines, you observe how this medicine affects you. Do not drive or use machines if you feel drowsy, dizzy, have blurred vision or double vision, or have difficulty concentrating. Be especially careful at the start of treatment, after a dose increase, after a change in formulation and/or when administered in combination with other medicines.

3. How to take Tramadol/Paracetamol Combix

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Before starting treatment and regularly during treatment, your doctor will explain what you can expect from the use of tramadol/paracetamol, when and for how long you should take it, when you should contact your doctor and when you should stop it (see also section 2).

You should take Tramadol/Paracetamol Combix for the shortest possible time. The dose should be adjusted to the intensity of the pain and your individual sensitivity. Normally, the lowest possible dose that produces pain relief should be used.

Use in children

This medicine is not recommended for use in children under 12 years of age.

Use in adults

Unless your doctor prescribes otherwise, the normal starting dose for adults and adolescents over 12 years of age is 2 tablets.

If necessary, the dose can be increased, as recommended by your doctor. The shortest interval between doses should be at least 6 hours.

Do not take more than 8 Tramadol/Paracetamol Combix tablets per day.

Do not take Tramadol/Paracetamol Combix more frequently than indicated by your doctor.

Your doctor may increase the interval between doses:

• If you are over 75 years old.
• If you have kidney problems.
• If you have liver problems.

Elderly patients

In elderly patients (over 75 years old), the elimination of tramadol may be slow. If this is your case, your doctor may recommend prolonging the dosing intervals.

Patients with liver or kidney failure/patients on dialysis

If you have severe liver or kidney disease, treatment with Tramadol/Paracetamol Combix is not recommended. If you have moderate liver or kidney disorders, your doctor may prolong the dosing intervals.

Method of administration

Tramadol/Paracetamol Combix is presented in the form of tablets for oral administration.

The tablets should be swallowed whole with sufficient liquid. They should not be broken or chewed.

If you think the effect of Tramadol/Paracetamol Combix is too strong (i.e., you feel very drowsy or have difficulty breathing) or too weak (i.e., you do not have adequate pain relief), tell your doctor.

If you take more Tramadol/Paracetamol Combix than you should

If you have taken more Tramadol/Paracetamol Combix than you should, even if you feel well, consult your doctor immediately, as there is a risk of serious liver damage that may only become apparent later.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Tramadol/Paracetamol Combix

If you forget to take a dose of Tramadol/Paracetamol Combix, it is likely that the pain will return. Do not take a double dose to make up for the missed doses, simply continue taking the tablets as usual.

If you stop taking Tramadol/Paracetamol Combix

Generally, no unwanted effects occur after stopping treatment with Tramadol/Paracetamol Combix. However, in rare cases, patients who have been taking Tramadol/Paracetamol Combix for a while and have stopped treatment abruptly may feel unwell (see section 4 "Possible side effects"). If you have been taking Tramadol/Paracetamol Combix for some time, you should consult your doctor before stopping treatment, as your body may have become accustomed to it.

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

4. Possible Adverse Effects

Like all medicines, Tramadol/Paracetamol Combix can produce adverse effects, although not all people suffer from them.

Very frequent: more than 1 in 10 treated people;

• nausea,
• dizziness, drowsiness.

Frequent: less than 1 in 10, but more than 1 in 100 treated people;

• vomiting, digestive problems (constipation, flatulence, diarrhea), stomach pain, dry mouth,
• itching, increased sweating,
• headache, agitation,
• confusion, sleep disorders, mood changes (anxiety, nervousness, euphoria - feeling of being "high-spirited" all the time-).

Infrequent: less than 1 in 100, but more than 1 in 1,000 treated people;

• tachycardia, hypertension, cardiac rhythm and frequency disorders,
• difficulty or pain when urinating,
• skin reactions (e.g., eruptions, hives),
• tingling sensation, numbness, or pinching sensation in the limbs, ringing in the ears, involuntary muscle spasms,
• depression, nightmares, hallucinations, (hearing, seeing or perceiving something that does not exist in reality), memory loss,
• difficulty swallowing, blood in the stool,
• chills, hot flashes, chest pain,
• difficulty breathing.

Rare: less than 1 in 1,000, but more than 1 in 10,000 treated people;

• seizures, difficulties in carrying out coordinated movements,
• addiction,
• blurred vision.

Frequency not known: the frequency cannot be estimated from the available data

• Decrease in blood sugar levels.
• Hypo.
• Serotonin syndrome, which can manifest through changes in mental state (e.g., agitation, hallucinations, coma), and other effects, such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle stiffness, lack of coordination and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "What you need to know before taking Tramadol/Paracetamol Combix").
• A serious disease that can make the blood more acidic (called metabolic acidosis) in patients with severe disease using paracetamol (see section 2).

The following recognized adverse effects have been reported by people who have taken medications containing only tramadol or only paracetamol. However, if you experience any of these symptoms while taking Tramadol/Paracetamol Combix, you should tell your doctor:

• Feeling of dizziness when standing up after being lying down or sitting, low heart rate, fainting, changes in appetite, muscle weakness, slower or weaker breathing, mood changes, changes in activity, changes in perception, worsening of asthma.
• In rare cases, skin rashes, being indicative of allergic reactions that can manifest through the sudden swelling of the face and neck, shortness of breath or drop in blood pressure and dizziness. If this happens to you, stop treatment and consult your doctor immediately. You should not take this medicine again.

In rare cases, using a medicine like tramadol can create dependence, making it difficult to stop taking it.

In rare cases, people who have been taking tramadol for some time may feel unwell if they stop treatment abruptly. They may feel agitated, anxious, nervous, or trembly. They may be hyperactive, have difficulty sleeping, and have digestive and intestinal disorders. Very few people may also have panic attacks, hallucinations, unusual perceptions such as itching, tingling, and numbness, and ringing in the ears (tinnitus). If you experience any of these symptoms after stopping treatment with Tramadol/Paracetamol Combix, please consult your doctor.

In exceptional cases, blood tests may reveal certain abnormalities, such as low platelet count, which can result in nosebleeds or bleeding in the gums.

The use of Tramadol/Paracetamol Combix along with anticoagulants (e.g., phenprocoumon, warfarin) may increase the risk of bleeding. You should inform your doctor immediately about any prolonged or unexpected bleeding.

Very rare cases of severe skin reactions have been reported.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Tramadol/Paracetamol Combix

It does not require special storage conditions.

Keep this medicine out of the sight and reach of children.

Store this medicine in a safe and protected place, where other people cannot access it. It can cause serious harm and be fatal to people who have not been prescribed it.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not use this medicine if you observe visible signs of deterioration.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines you no longer need in the SIGRE Point of the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Packaging Content and Additional Information

Composition of Tramadol/Paracetamol Combix

• The active ingredients are tramadol hydrochloride and paracetamol.

Each film-coated tablet contains 37.5 mg of tramadol hydrochloride and 325 mg of paracetamol.

• The other components are: pregelatinized corn starch, corn starch, sodium starch glycolate, microcrystalline cellulose (E460i), magnesium stearate (E470b), coating agent (hypromellose (E464), titanium dioxide (E171), macrogol (1521), talc (E553b)).

Appearance of the Product and Packaging Content

Tramadol/Paracetamol Combix film-coated tablets are presented in the form of a film-coated tablet, white in color, with a capsule shape, biconvex, with the mark "334" engraved on one face and smooth on the other.

The Tramadol/Paracetamol Combix tablets are packaged in PVC/PVDC-Aluminum blisters in packs of 20 or 60 tablets.

Only some pack sizes may be marketed.Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz, 2. Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC les Hautes Patures

Parc d’activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Date of the Last Revision of this Prospectus:February 2025.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.