Package Leaflet: Information for the Patient

Zytram 400 mg prolonged-release tablets

Tramadol hydrochloride

Read this leaflet carefully before you start taking this medicinebecause it contains important information for you.

• 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 only. Do not pass it on to others even if their symptoms are the same as yours. It may harm them.
• If you experience any side effects, talk to your doctor or pharmacist. See section 4.

1. What Zytram tablets are and what they are used for

2. What you need to know before you start taking Zytram tablets

3. How to take Zytram tablets

4. Possible side effects

5. Storage of Zytram tablets

6. Contents of the pack and additional information

These tablets have been prescribed by your doctor for the treatment of moderate to severe pain for a period of 24 hours. The tablets contain tramadol as the active ingredient, which is a potent analgesic (pain reliever), belonging to a group of medicines called opioids.

These tablets are only for use in adults and adolescents over 12 years old.

Do not take Zytram tablets

• If you are allergic to tramadol or any of the other ingredients of this medicine (listed in section 6);
• If you have taken excessive alcohol or higher doses than recommended of sleeping pills, painkillers, or psychotropic medications (used to treat psychiatric or mental disorders);
• If you are taking monoamine oxidase inhibitors (e.g. tranilcipromina, fenelzina, isocarboxazida, mocoblemida, and linezolid), or if you have taken this type of medication in the last two weeks;
• To treat withdrawal syndrome caused by stopping another potent analgesic.

Warnings and precautions

Consult your doctor or pharmacist before starting to take these tablets if:

• You have or have had a history of addiction to alcohol or drugs;
• You have or have had epilepsy, seizures, tremors, or convulsions;
• You have severe headaches, or you are feeling unwell due to a head injury, or you have high intracranial pressure (e.g. due to a brain pathology). The tablets may worsen symptoms or mask a head injury;
• You have severe liver or kidney disease;
• You are in shock (you suddenly feel very dizzy, tired, cold, trembling, and pale);
• You have slow and shallow breathing (respiratory depression);
• You are depressed and taking antidepressants, as some may interact with tramadol (see "Other medicines and Zytram prolonged-release tablets");
• You have constipation;

Respiratory disorders related to sleep

Zytram tablets may cause respiratory disorders related to sleep such as central sleep apnea (pause in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). These symptoms may include pause in breathing during sleep, nocturnal awakening due to difficulty breathing, difficulty maintaining sleep, or excessive daytime somnolence. If you or someone else observes these symptoms, consult your doctor. Your doctor may consider reducing the dose.

Tolerance, dependence, and addiction

This medicine contains tramadol, which is an opioid. Repeated use of opioids can make the medication less effective (you become accustomed to it, known as tolerance). Repeated use of Zytram may also cause dependence, abuse, and addiction, which can lead to a potentially fatal overdose. The risk of these side effects may increase with higher doses and longer use.

Dependence or addiction may make you feel like you no longer have control over the amount of medication you take or how often you take it.

The risk of becoming dependent or addicted varies from person to person. You may be at a higher risk of becoming dependent or addicted to Zytram if:

- You or a family member has a history of alcohol abuse or dependence.

- You are a smoker.

- You have had problems with your mood (depression, anxiety, or personality disorder) or have received treatment from a psychiatrist for other mental health conditions.

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

- You need to take the medication for longer than recommended by your doctor.

- You need to take more doses than recommended.

- You are using the medication for reasons other than those prescribed, such as "to calm down" or "to help you sleep".

- You have made repeated and unsuccessful attempts to stop or control the use of the medication.

- You do not feel well when you stop taking the medication, and you feel better when you take it again ("withdrawal symptoms").

If you notice any of these signs, talk to your doctor to address the best treatment strategy for your case, including when it is appropriate to stop taking it and how to do it safely (see section 3, "If you stop taking Zytram").

Tramadol is metabolized in the liver by an enzyme. Some people have a variation of this enzyme, and this can affect each person differently. In some people, it may not be possible to achieve sufficient pain relief, while others may be more likely to experience severe adverse effects. If you notice any of the following adverse effects, 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.

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 experience any of the symptoms linked to this severe syndrome (see section 4 "Possible adverse effects").

Consult your doctor or pharmacist if you experience any of the following symptoms while taking Zytram: extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. This may indicate that you have adrenal insufficiency (low cortisol levels). If you experience any of these symptoms, report them to your doctor, who will decide if you should take a hormone supplement.

Occasionally, increased sensitivity to pain (hyperalgesia) may occur, which does not respond to an additional increase in the tramadol dose, especially at high doses. You may need to reduce the tramadol dose or switch to an alternative opioid.

Children and adolescents

Use in children with respiratory problems

Tramadol should not be used in children with respiratory problems, as the symptoms of tramadol toxicity may worsen in these children.

Other medicines and Zytram prolonged-release tablets

Inform your doctor or pharmacist if you are taking or have taken recently or may need to take any other medication. If you are taking other medications with these tablets, the effect of these tablets or the other medication may be altered.

The concomitant use of Zytram and sedatives such as benzodiazepines or related medications increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be fatal. Therefore, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes Zytram with sedatives, your doctor should limit the dose and duration of concomitant treatment.

Inform your doctor about all sedatives you are taking and follow your doctor's recommendations regarding the dose. It may be helpful to inform friends or family members about the signs and symptoms mentioned above. Inform your doctor when you experience such symptoms.

These tablets should not be used concomitantly with a monoamine oxidase inhibitor (MAOI), or if you have been taking this type of medication in the last 2 weeks (see section 2 "Do not take Zytram tablets").

The risk of adverse effects increases:

• If you are taking medications that can cause seizures, such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take Zytram tablets at the same time. Your doctor will inform you if Zytram tablets are suitable for you.
• If you are taking certain antidepressants. Zytram tablets may interact with these medications and you may experience a serotonin syndrome (see section 4 "Possible adverse effects").

Inform your doctor or pharmacist if you are taking:

• Sleeping pills (tranquilizers, hypnotics, or sedatives);
• Carbamazepine to treat seizures, tremors, convulsions, and some types of pain;
• Antidepressants;
• Medications to treat psychiatric or mental disorders;
• Ritonavir to treat HIV;
• Digoxin to treat heart failure or arrhythmias;
• Other potent analgesics (buprenorphine, nalbuphine, and pentazocine);
• Certain morphine-like medications, such as to treat cough or to treat withdrawal syndrome;
• Barbiturates to treat seizures or to sleep;
• Benzodiazepines, to treat anxiety or to sleep;
• Gabapentin or pregabalin to treat epilepsy or pain due to nerve problems (neuropathic pain);
• Certain medications to prevent blood clotting or to thin the blood (anticoagulant coumarins, such as warfarin);
• Ondansetron, to treat nausea or general discomfort.

Taking Zytram tablets with alcohol

Consult your doctor or pharmacist if you ingest or intend to ingest alcohol while taking this medication.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Do not take this medication if you are pregnant. Depending on the dose and duration of tramadol treatment, the newborn may experience slow and shallow breathing (respiratory depression) or withdrawal symptoms.

Breastfeeding

Tramadol is excreted in breast milk. Therefore, do not take Zytram more than once during breastfeeding, or if you take Zytram more than once, stop breastfeeding.

Babies born to mothers who have used Zytram prolonged-release tablets during pregnancy may experience withdrawal symptoms, including loud crying, irritability, restlessness, agitation (trembling), feeding difficulties, and sweating.

Driving and operating machinery

These tablets may cause a range of side effects, such as drowsiness, blurred vision, and dizziness, which may affect your ability to drive or operate machinery (see section 4 for a complete list of side effects). These effects are more noticeable when you start taking the tablets, or when your dose is increased. If you are affected, do not drive or operate machinery.

Zytram tablets contain lactose

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, ask your doctor or pharmacist. Before starting treatment and regularly during treatment, your doctor will discuss with you what you can expect from the use of Zytram, when and for how long you should take it, when to contact your doctor and when to discontinue it (see also section 2).

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.

Adults and adolescents over 12 years

The usual initial dose is one 150 mg tablet once a day. However, your doctor will prescribe the required dose to treat the pain you are experiencing. Do not exceed the dose recommended by your doctor. If you find that you still feel pain while taking the tablets, consult your doctor. Generally, you should not take more than 400 mg per day.

The tablets should be swallowed whole with water.Do not break, dissolve or chew.

Zytram tablets is designed to adequately cover treatment over 24 hours when taken whole. If the tablet is broken, crushed or dissolved or chewed, the full 24-hour dose may be absorbed rapidly by your body, which can be hazardous and cause serious problems such as an overdose that can be fatal.

You should take the tablets at the same time every day. For example, if you have taken a tablet at 8 am, you should take the next tablet at 8 am the next day.

Older patients

In older patients (over 75 years), the elimination of tramadol may be slow. If this is your case, your doctor may recommend reducing the dose.

Patients with liver or kidney disease/patients on dialysis

If you have any severe liver or kidney disease, treatment with Zytram tablets is not recommended. If you have mild or moderate liver or kidney disease, your doctor may recommend reducing the dose.

Children under 12 years

Children under 12 years should not take this medication.

If you take more Zytram tablets than you should or someone takes them by accident

Contact your doctor or the nearest hospital immediately. People who have taken an overdose may experience excessive sleepiness, feel very unwell or very dizzy. They may suffer from seizures, tremors or convulsions. They may also have breathing difficulties that can lead to loss of consciousness or even death and may require emergency treatment in the hospital. In case of requiring medical attention, make sure to bring this leaflet and the rest of the tablets with you.

In case of overdose or accidental ingestion, consult the Toxicological Information Service (Tel. 91.562.04.20), indicating the product and the amount ingested.

If you forget to take Zytram tablets

If you remember within the next 10 hours from the time when the tablet should have been taken, take the missed tablet immediately. Then take the next tablet at the usual time. If more than 10 hours have passed, it is best to consult your doctor.

Do not take a double dose to compensate for the missed dose.

If you interrupt treatment with Zytram tablets

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 discontinue it, which can be done by gradually reducing the dose to reduce the likelihood of unnecessary side effects (withdrawal symptoms). If you stop taking these tablets suddenly, withdrawal symptoms such as agitation, anxiety, nervousness, difficulty falling asleep, unusual hyperactivity, tremors or gastrointestinal disturbances, e.g. stomach upset, may occur.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

All medicines can cause allergic reactions, even though severe allergic reactions are rare. Contact your doctor immediately if you suddenly experience shortness of breath, difficulty breathing, swelling of the eyelids, face, or lips, or a particular itching sensation, especially if it affects the entire body.

The most severe side effect is that in which slower or weaker breathing is observed (respiratory depression).

Like with all powerful analgesics, there is a risk of addiction or dependence on these tablets.

Very common:may affect more than 1 in 10 patients

Common:may affect up to 1 in 10 patients

Uncommon:may affect up to 1 in 100 patients

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

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

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

• Respiratory problems during sleep (sleep apnea syndrome).
• • Decreased blood sugar level
  • Unusual feeling of weakness
  • Hiccup
  • Need to take increasingly higher doses of the tablets to achieve the same level of pain relief (tolerance).
  • Symptoms of withdrawal in babies born to mothers who have used tramadol during pregnancy (see section 2 "Pregnancy, breastfeeding, and fertility").
  • Increased sensitivity to pain.
  • Serotonin syndrome, which may 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 Zytram prolonged-release tablets").

In some cases, the tablet matrix may be observed in the stool, which does not affect the efficacy of the tablets.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is not listed in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Usehttps://www.notificaram.es.

By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Do not take these tablets after the expiration date that appears on the blister pack and the box. The expiration date is the last day of the month indicated.

Do not store above 86°F (30°C).

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. This will help protect the environment.

Composition of Zytram tablets

The active ingredient is hydrochloride of tramadol. Each tablet contains 400 mg of hydrochloride of tramadol.

The other components are:

Appearance of the product and contents of the packaging

This medication is presented in the form of coated tablets, white in color, oval-shaped, marked with a T followed by the dosage (400), with an approximate length of 19 mm.

Each box contains 2, 7, 10, 14, 15, 20, 28, 30, 50, 56, 60 or 100 tablets.

Some packaging sizes may only be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Mundipharma Pharmaceuticals, S.L.

Bahía de Pollensa, 11

28042 Madrid

Spain

Responsible for manufacturing

Mundipharma DC B.V.

Leusderend 16

3832 RC Leusden

Netherlands

or

Zambón Switzerland LTD

Via Industria, 13 (Campedino)

CH-6814 – Switzerland

or

MEDA Pharma GmbH & Co. KG

Benzstrasse 1

61352 Bad Homburg

Germany

This medication is authorized in the member states of the European Economic Area with the following names:

AustriaAdamon®long retard - Filmtabletten

PortugalTRAVEX®Long

SpainZytram®

Date of the last review of this leaflet:May 2024

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/