Leaflet: information for the user

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

Tramadol hydrochloride/Paracetamol

Read this leaflet carefully before you start to take this medicine, because it contains important information for you.

-Keep this leaflet, as 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, and you must not give it to others, even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Tramadol/Paracetamol Combix is a combination of two analgesics: tramadol and paracetamol, which act together to relieve pain.

Tramadol/Paracetamol Combix is indicated for the symptomatic treatment of moderate to intense pain whenever your doctor believes that the combination of tramadol and paracetamol is necessary.

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

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 sleeping pills, 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 indicative 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, intense headaches associated with vomiting,
• if you have dependence on any other pain-relieving medicine, for example morphine,
• if you are taking other pain-relieving medicines 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").

Inform your doctor immediately if you experience any of the following during treatment with Tramadol / Paracetamol Combix:

if you have severe diseases, such as severe kidney failure or sepsis (when bacteria and their toxins circulate in the blood, causing damage to organs), or if you have malnutrition, chronic alcoholism or if you are also taking flucloxacillin (an antibiotic). A serious disease called metabolic acidosis (a blood and fluid anomaly) has been reported in patients in these situations when using paracetamol at regular doses for a prolonged period or when taking paracetamol with flucloxacillin. 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 become tolerant of it, known as tolerance). Repeated use of tramadol / paracetamol can also cause dependence, abuse and addiction, which can lead to a potentially fatal overdose. The risk of these side effects may increase with a higher dose and longer use.

Dependence or addiction can make you feel like 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 to tramadol / paracetamol varies from person to person. You may have a higher risk of becoming dependent or addicted to tramadol / paracetamol if:

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

If you notice any of the following 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 of the recommended dose
• You use the medicine for reasons other than those prescribed, for example, "to stay calm" or "to sleep"
• You have tried repeatedly and unsuccessfully 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 to get advice on the best course of treatment for you, including when it is appropriate to stop taking it and how to do it safely (see section 3, If you interrupt treatment with Tramadol / Paracetamol Combix).

Respiratory problems related to sleep

Tramadol / Paracetamol Combix may cause respiratory problems related to sleep, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood).Between the symptoms may include pauses in breathing during sleep, nocturnal awakenings due to lack of breath, difficulty maintaining sleep or excessive daytime somnolence. If you or someone else observes these symptoms, contact your doctor. Your doctor 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 indicative of adrenal insufficiency (low cortisol levels). If you have these symptoms, contact your doctor, who will decide if you need to take hormone supplements.

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

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

Taking Tramadol / Paracetamol Combix with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine.

• Gabapentin or pregabalin for treating epilepsy or pain due to nerve problems (neuropathic pain).

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

You should not takeTramadol / Paracetamol Combixwith monoamine oxidase inhibitors (MAOIs) (see "Do not take Tramadol / Paracetamol Combix").

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

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

• Carbamazepine (medicine normally used to treat epilepsy or some 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 migraine treatment) or selective serotonin reuptake inhibitors, "SSRIs" (for depression treatment). If you experience confusion, agitation, fever, sweating, uncoordinated limb or eye movements, involuntary muscle contractions or diarrhea, you should call your doctor.
• Sedatives, sleeping pills, other analgesics such as morphine and codeine (also when used for cough treatment), baclofen (muscle relaxant), some blood pressure-lowering medicines, antidepressants or allergy medicines. You may feel drowsy or dizzy. If this occurs, consult your doctor.
• Antidepressants, anesthetics, neuroleptics (medicines that affect mood) or bupropion (medicine used as a smoking cessation aid). The risk of having a seizure may increase. Your doctor will tell you if Tramadol / Paracetamol Combix is suitable for you.
• Warfarin or phenprocoumon (medicine used to prevent blood clots). The effectiveness of these medicines may be altered, with a risk of bleeding. You should inform your doctor immediately of any prolonged or unexpected bleeding.
• If you are taking medicines that facilitate or may cause seizures, such as certain antidepressants or antipsychotics. The risk of seizures increases if you take Tramadol / Paracetamol Combix simultaneously with these medicines. Your doctor will tell you if Tramadol / Paracetamol Combix is suitable for you.
• If you are taking medicines for depression treatment. Tramadol / Paracetamol Combix may interact with these medicines and may experience a serotonin syndrome (see section 4 "Possible side effects").

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

• Metoclopramide, domperidone or ondansetron (medicines for nausea and vomiting treatment),
• Colestiramine (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 take alcohol while taking Tramadol / Paracetamol Combix.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using 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.

Lactation

Tramadol may pass into breast milk. For this reason, you should not take Tramadol / Paracetamol Combix more than once during breastfeeding or, 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 essential to observe how this medicine affects you before driving or using machines. 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 increasing the dose, after changing the formulation and/or when taking it with other medicines.

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

Before starting treatment and regularly during it, 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 interrupt it (see also section 2).

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

Use in children

This medication is not recommended for use in children under 12 years old.

Use in adults

Unless your doctor prescribes something different, the usual starting dose for adults and adolescents over 12 years old is 2 tablets.

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

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

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

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.

Older patients

In older 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 insufficiency/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 problems, your doctor may prolong the dosing intervals.

Administration form

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 estimate that the effect of Tramadol/Paracetamol Combix is too strong (i.e., you feel very drowsy or have difficulty breathing) or weak (i.e., you do not have adequate pain relief), inform 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 severe liver damage that will only become apparent later.

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

If you forgot to take Tramadol/Paracetamol Combix

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

If you interrupt treatment with Tramadol/Paracetamol Combix

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

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

Like all medicines, Tramadol/Paracetamol Combix can cause side effects, although not everyone will experience them.

Very common:more than 1 in 10 people treated;

• nausea,
• dizziness, drowsiness.

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

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

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

• tachycardia, hypertension, heart rhythm and frequency disorders,
• difficulty or pain urinating,
• skin reactions (e.g. rashes, urticaria),
• tingling, numbness, or pins and needles sensation in the extremities, ear noises, 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 people treated;

• seizures, difficulties with coordinated movements,
• addiction,
• blurred vision.

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

- Decreased blood sugar levels.

- Hiccups.

- Serotonin syndrome, which can manifest as 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 rigidity, 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 (designated metabolic acidosis) in seriously ill patients using paracetamol (see section 2).

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

• Dizziness when standing up after lying down or sitting, low heart rate, fainting, changes in appetite, muscle weakness, slower or shallower breathing, mood changes, changes in activity, changes in perception, worsening of asthma.
• In rare cases, skin eruptions, indicating allergic reactions that can manifest as sudden swelling of the face and neck, shortness of breath, or a drop in blood pressure and dizziness. If this happens, stop treatment and consult your doctor immediately. Do not take this medicine again.

In rare cases, using a medicine like tramadol, can make you dependent, making it difficult to stop taking it.

In rare instances, people who have been taking tramadol for some time may feel unwell if they stop treatment abruptly. They may feel agitated, anxious, nervous, or shaky. They may be hyperactive, have difficulty sleeping, and experience gastrointestinal and intestinal problems. Very few people may also experience panic attacks, hallucinations, unusual perceptions such as itching, tingling, and numbness, and ear noises (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 a low platelet count, which can cause nasal or gum bleeding.

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

Severe skin reactions have been reported very rarely.

Reporting of side effects

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

This product does not require special storage conditions.

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

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

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

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and unused medication at the SIGRE drop-off point at the pharmacy. Ask your pharmacist how to dispose of unused packaging and medication. This will help protect the environment.

Composition of Tramadol/Paracetamol Combix

• The active principles 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: Maize pregelatinized starch, maize 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 content of the packaging

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

The film-coated tablets of Tramadol/Paracetamol Combix are packaged in blisters, PVC/PVDC-Aluminium in containers of 20 or 60 tablets.

Only some package sizes may be commercially marketed.Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Laboratorios Combix, S.L.U.

C/ Badajoz, 2. Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

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

Last review date of this leaflet:February 2025.

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