Package Leaflet: Information for the User

Tramadol Retard Combix 200 mg prolonged-release tablets EFG

Tramadol hydrochloride

Read this leaflet carefully before you start taking this medicine.

• Keep this leaflet, as 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 pass it on to others even if their symptoms are the same. It may harm them.
• If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.

1. What Tramadol Retard Combix is and what it is used for

2. Before taking Tramadol Retard Combix

3. How to take Tramadol Retard Combix

4. Possible side effects

5. Storage of Tramadol Retard Combix

6. Further information

Tramadol is an analgesic belonging to the opioid group that acts on the central nervous system. It relieves pain by acting on specific nerve cells in the spinal cord and brain.

Tramadol Retard is indicated for the treatment of moderate to intense pain.

Do not take Tramadol Retard Combix

• If you are allergic (hypersensitive) to tramadol or any of the other components of Tramadol Retard Combix.
• In case of acute intoxications caused by alcohol, sleep-inducing medications, analgesics, or psychotropic drugs (medications that act on the mood and emotions).
• If you are also taking MAO inhibitors (certain medications used to treat depression) or if you have taken them in the last 14 days before starting treatment with Tramadol Retard Combix (see "Use of other medications").
• If you have epilepsy and your seizures are not adequately controlled with treatment.
• As a treatment for withdrawal syndrome.

Be especially careful with Tramadol Retard Combix

• If you think you are dependent on other analgesics (opioids).
• If you experience disorders of consciousness (if you think you are going to faint).
• If you are in a state of shock (a sign of this state may be cold sweat).
• If you have an increase in pressure within the skull (for example, after a head trauma or brain disease).
• If you have difficulty breathing.
• If you are epileptic or have seizures, because the risk of these seizures may increase.
• If you have any liver or kidney disease.
• If you suffer from depression and are taking antidepressants, as they may interact with tramadol (see "Use of other medications").

Please consult your doctor before taking the medication in such cases.

Warnings and precautions

Tramadol is transformed in the liver by an enzyme. Some people have a variation of this enzyme and this may affect each person differently. In some people, it may be possible to achieve insufficient relief from pain, while others may be more likely to experience severe adverse effects. If you notice any of the following adverse effects, you should stop taking this medication and consult a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, general discomfort or vomiting, constipation, loss of appetite.

Seizures have been reported in patients taking tramadol at the recommended dose. The risk may increase when the tramadol dose exceeds the recommended daily limit (400 mg).

Tolerance, dependence, and addiction

This medication contains tramadol, which is an opioid medication. Repeated use of opioids can make the medication less effective (the body becomes accustomed to it, known as pharmacological tolerance). Repeated use of tramadol can also lead to dependence, abuse, and addiction, which could lead to a potentially fatal overdose. The risk of these adverse effects may be higher with a higher dose and longer use.

Dependence or addiction can cause a feeling of lack of control over the amount of medication you should use or the frequency with which you should use it.

The risk of dependence or addiction varies from person to person. The risk of becoming dependent or addicted to tramadol may be higher if:

• You or any member of your family have abused alcohol or experienced dependence on it, prescription medications, or illegal drugs ("addiction").
• You are a smoker.
• You have had any problems with mood (depression, anxiety, or personality disorder) or have followed treatment with a psychiatrist for other mental health conditions.

If you notice any of the following symptoms while using tramadol, it could be a sign of dependence or addiction:

• You need to use the medication for a longer period than indicated by your doctor.
• You need to use a higher dose than recommended.
• You are using the medication for reasons other than those prescribed, for example, "to feel calm" or "to help you sleep".
• You have made repeated and unsuccessful attempts to stop using the medication or control its use.
• You feel unwell when you stop using the medication, and you feel better once you take it again ("withdrawal symptoms").

If you notice any of these signs, consult your doctor to determine the best course of treatment for you, when it is appropriate to stop taking the medication, and how to do it safely (see section 3, if you interrupt treatment with Tramadol Retard Combix).

Respiratory disorders related to sleep

Tramadol Retard Combix may cause respiratory disorders related to sleep, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Among 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.

Consult your doctor or pharmacist if you experience any of the following symptoms while taking Tramadol Retard 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 hormone supplements.

Also inform your doctor if any of the following problems occur during treatment with Tramadol Retard Combix or if they have occurred at any time.

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 monotherapy. Consult your doctor immediately if you experience any of the symptoms linked to this severe syndrome (see section 4 "Possible adverse effects").

Children and adolescents

Use in children with respiratory problems

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

Use of other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, even those purchased without a prescription.

It is recommended to avoid simultaneous treatment of Tramadol Retard Combix with monoamine oxidase inhibitors (MAOIs) (certain medications for the treatment of depression).

The analgesic effect of Tramadol Retard Combix and its duration may be reduced if you take medications that contain:

• Carbamazepine (for epilepsy)
• Pentazocine, nalbuphine, or buprenorphine (analgesics);
• Ondansetron (medication to prevent nausea)

Your doctor will indicate if you should take Tramadol Retard Combix and at what dose.

The risk of adverse effects increases,

• If you take tranquilizers, sleep-inducing medications, other analgesics such as morphine and codeine (also when used for cough), and alcohol while taking Tramadol Retard Combix. It may cause more sleep or the sensation of fainting. If this occurs, consult your doctor.

• If you are taking medications that may cause seizures, such as some antidepressants. The risk of seizures may increase if you take Tramadol Retard Combix at the same time. Your doctor will tell you if Tramadol Retard Combix is suitable for you.

• If you are taking selective serotonin reuptake inhibitors (SSRIs) or MAO inhibitors (medications used to treat depression). Tramadol Retard Combix may interact with them and may lead to a serotonin syndrome (see section 4 "Possible adverse effects").

• If you take anticoagulant coumarins (medications that prevent abnormal blood coagulation), such as warfarin, along with Tramadol Retard Combix. The effect of these medications on blood coagulation may be affected and may lead to bleeding.

• If you take gabapentin or pregabalin to treat epilepsy or pain due to nerve problems (neuropathic pain).

Tramadol Retard Combix with food and drinks

Do not consume alcohol during treatment with Tramadol Retard Combix, as its effect may be intensified. Food does not affect the effect of Tramadol Retard Combix.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

There is very little information about the safety of tramadol during human pregnancy. Therefore, you should not take Tramadol Retard Combix if you are pregnant.

Long-term use during pregnancy may lead to withdrawal syndrome in newborns.

Generally, tramadol is not recommended for use during breastfeeding.Tramadol is excreted in breast milk. Therefore, you should not take Tramadol Retard Combix more than once during breastfeeding, or if you take Tramadol Retard Combix more than once, you should stop breastfeeding.

Driving and operating machines

Ask your doctor if you can drive or operate machines during treatment with Tramadol Retard Combix. It is essential to observe how this medication affects you before driving or operating machines. Do not drive or operate machines if you feel drowsy, dizzy, have blurred vision, or have difficulty concentrating. Be especially careful when administering it with other medications.

Follow exactly the administration instructions for Tramadol Retard Combix as indicated by your doctor.

Consult your doctor or pharmacist if you have any doubts.

Before starting treatment and regularly during it, your doctor will also explain what you can expect from the use of Tramadol Retard Combix, when and for how long you should use it, when you should contact your doctor and when you should discontinue use (see also section 2).

The dose should be adjusted according to the intensity of the pain and individual sensitivity to pain. In general, the lowest analgesic dose should be taken.

Unless your doctor has given you different instructions, the usual dose is:

Adults and adolescents over 12 years old

A Tramadol Retard Combix 100 mg prolonged-release tablet twice a day (equivalent to 200 mg of tramadol hydrochloride per day), preferably in the morning and at night.

Your doctor may prescribe a different and more suitable dose of this medication if necessary.

If necessary, the dose can be increased to 150 mg or 200 mg twice a day (equivalent to 300 mg - 400 mg of tramadol hydrochloride per day).

Do not take more than 400 mg of tramadol hydrochloride per day, unless your doctor has instructed you otherwise.

Children

Tramadol Retard Combix is not suitable for children under 12 years old.

Older patients

In elderly patients (over 75 years old), tramadol elimination may be slower. If this occurs, your doctor may prolong the dosing intervals.

Patients with liver or kidney insufficiency / dialysis

Patients with severe liver or kidney insufficiency should not take Tramadol Retard Combix. If your liver or kidney insufficiency is mild or moderate, your doctor may prolong the dosing interval.

How and when to take Tramadol Retard Combix?

Tramadol Retard prolonged-release tablets are administered orally.

Always swallow the Tramadol Retard Combix tablets whole, not divided or chewed, with sufficient liquid, preferably in the morning and at night. You can take the tablet with an empty stomach or with meals.

For how long should you take Tramadol Retard Combix?

Tramadol Retard Combix should not be administered for longer than strictly necessary.

If you require prolonged treatment, your doctor will monitor you at short and regular intervals (if necessary with interruptions in treatment) to see if you should continue treatment with Tramadol Retard Combix and at what dose.

If you estimate that the effect of this medication is too strong or too weak, inform your doctor or pharmacist.

If you take more Tramadol Retard Combix than you should

If you have taken Tramadol Retard Combix by mistake more than you should, generally you will not have any negative effects. Take the next dose as prescribed.

After taking very high doses, you may experience pupil constriction, vomiting, decreased blood pressure, increased heart rate, collapse, decreased level of consciousness to coma (deep unconsciousness), seizures, and difficulty breathing that can lead to respiratory arrest. In this case, inform your doctor immediately.

If you forget to take Tramadol Retard Combix

If you forget to take the tablets, it is likely that the pain will return. Do not take a double dose to compensate for the missed doses, simply continue treatment as instructed by your doctor.

If you interrupt treatment with Tramadol Retard Combix

You should not stop taking this medication suddenly unless your doctor tells you to. If you want to stop taking your medication, talk to your doctor first, especially if you have been taking it for a long time. Your doctor will inform you when and how to stop it, which can be done by gradually reducing the dose to reduce the likelihood of unnecessary adverse effects (withdrawal symptoms).

Generally, no undesirable effects occur when treatment with Tramadol Retard Combix is discontinued. However, in rare cases, when some people who have been taking Tramadol Retard Combix for some time stop taking it suddenly, they may feel unwell. They may feel agitated, anxious, nervous, or shaky. They may feel hyperactive, have difficulty sleeping, or experience gastrointestinal or intestinal disorders. Very few people may experience panic attacks, hallucinations, unusual perceptions such as itching, tingling, and numbness, and ringing in the ears (tinnitus). Rarely, other unusual central nervous system symptoms, such as confusion, delirium, distorted perception of one's own personality (derealization), and altered perception of reality (depersonalization) and delusions of persecution (paranoia), have been seen. If you experience any of these symptoms after stopping Tramadol Retard Combix, please consult your doctor. If you have any doubts about the use of this medication, consult your doctor or pharmacist.

Like all medicines, Tramadol Retard Combix may cause side effects, although not everyone will experience them. The frequency of side effects is usually classified as follows:

• Very common (affecting more than 1 in 10 people)
• Common (affecting more than 1 in 100 people and less than 1 in 10 people)
• Uncommon (affecting more than 1 in 1,000 people and less than 1 in 100 people)
• Rare (affecting more than 1 in 10,000 people and less than 1 in 1,000 people)
• Very rare (affecting less than 1 in 10,000 people)
• Frequency not known (cannot be estimated from available data)

You should consult your doctor immediately if you experience symptoms of an allergic reaction such as swelling of the face, tongue, and/or throat and/or difficulty swallowing and hives accompanied by difficulty breathing.

The most common side effects during treatment with Tramadol Retard are nausea and dizziness, which occur in more than 1 in 10 patients.

Indeterminate frequency (cannot be estimated from available data)

Serotonin syndrome, which may manifest as changes in mental state (such as 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 (such as nausea, vomiting, diarrhea) (see section 2 "Before taking Tramadol Retard Combix").

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 the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep out of reach and sight of children.

Store this medication in a safe and protected place, inaccessible to others. This medication may cause severe and potentially fatal harm to individuals not prescribed it.

This medication does not require special storage conditions.

Do not use Tramadol Retard Combix after the expiration date appearing on the box and blister pack after "CAD". The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or trash. Dispose of packaging and unused medications at the SIGRE collection point at the pharmacy. If unsure, ask your pharmacist how to properly dispose of packaging and unused medications. This will help protect the environment.

Composition of Tramadol Retard Combix

The active ingredient is tramadol hydrochloride. Each tablet contains 200 mg of tramadol hydrochloride.

The other components are:

Tablet core: microcrystalline cellulose, polyethylene oxide, povidone, and magnesium stearate.

Tablet coating: hypromellose, titanium dioxide (E171), macrogol, talc, yellow iron oxide (E172), red iron oxide (E172), and quinoline yellow (E104) lake.

Appearance of the product and contents of the package

Tramadol Retard Combix 200 mg prolonged-release tablets are brownish-colored, round, biconvex tablets with the mark “200” printed on one face and smooth on the other.

Tramadol Retard Combix 200 mg is packaged in blisters containing 20 or 60 prolonged-release tablets.

Tramadol Retard Combix is also available in prolonged-release tablets of 100 and 150 mg in packages containing 20 or 60 tablets.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Combix Laboratories, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible manufacturer

Zydus France

25, parc d’activités des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

This leaflet was approved in June 2024

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