ZYTRAM BID 75 mg PROLONGED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the Patient

Zytram BID 75 mg prolonged-release tablets

Tramadol Hydrochloride

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 thepackage leaflet

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

1. What is Zytram BID tablets and what is it used for

These tablets have been prescribed for you by your doctor to relieve moderate to severe pain over a period of 12 hours. The tablets contain tramadol as the active substance, which is a potent pain reliever (or painkiller), belonging to a group of medicines called opioids.

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

2. What you need to know before you take Zytram BID tablets.

Do not take Zytram BID tablets

• If you are allergic to tramadol or any of the other ingredients of this medicine (listed in section 6);
• If you have taken too much alcohol or more than the recommended dose of sleeping pills, painkillers, or psychotropic medicines (used to treat psychiatric or mental disorders);
• If you are taking monoamine oxidase inhibitors (e.g. tranylcypromine, phenelzine, isocarboxazid, moclobemide, and linezolid), or if you have taken this type of medicine in the last 2 weeks;
• To treat withdrawal symptoms caused by stopping another potent painkiller.

Warnings and precautions

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

• You have or have had any type of addiction to alcohol or drugs;
• You have or have had epilepsy, seizures, tremors, or convulsions;
• You have or have had severe headaches, or feel unwell due to a head injury, or have increased intracranial pressure (e.g. due to a brain disease). The tablets may worsen the 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 weak breathing (respiratory depression);
• You suffer from depression and are taking antidepressants, as some may interact with tramadol (see "Other medicines and Zytram BID prolonged-release tablets");
• You suffer from constipation.

Respiratory disorders related to sleep

Zytram BID tablets may cause sleep-related respiratory disorders such as central sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). These symptoms may include pauses in breathing during sleep, nocturnal awakenings due to difficulty breathing, difficulty maintaining sleep, or excessive daytime sleepiness. 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 medicine. Repeated use of opioids can make the medicine less effective (you get used to it, which is known as tolerance). Repeated use of Zytram BID can also lead to dependence, abuse, and addiction, which can cause a potentially life-threatening overdose. The risk of these side effects may increase with higher doses and longer treatment duration.

Dependence or addiction can make you feel that you no longer have control over 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 be at higher risk of becoming dependent or addicted to Zytram BID if:

• You or someone in your family has a history of alcohol or drug abuse. You are a smoker. You have ever had problems with your mood (depression, anxiety, or personality disorder) or have received psychiatric treatment for other mental illnesses.

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

• You need to take the medicine for longer than recommended by your doctor.
• You need to take more doses than recommended.
• You are using the medicine for reasons other than those prescribed, for example, "to calm down" or "to help you sleep".
• You have made repeated attempts to stop or control the use of the medicine without success.
• You do not feel well when you stop taking the medicine and 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 in 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 BID).

Consult your doctor or pharmacist if you experience any of the following symptoms while taking Zytram BID: 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, inform your doctor, who will decide whether you need to take a hormonal supplement.

Tramadol is transformed in the liver by an enzyme. Some people have a variation of this enzyme, and this can affect each person differently. In some people, sufficient pain relief may not be achieved, while others are more likely to experience serious side effects. If you notice any of the following side effects, you must stop taking this medicine and consult a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, general malaise, or vomiting, constipation, loss of appetite.

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

There is a weak risk that you may experience a serotonergic 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 associated with this serious syndrome (see section 4 "Possible side effects").

Children and adolescents

Use in children with respiratory problems

The use of tramadol is not recommended in children with respiratory problems, as the symptoms of tramadol toxicity can worsen in these children.

Other medicines and Zytram BID prolonged-release tablets

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines. If you are taking other medicines with these tablets, the effect of these tablets or the other medicine may be altered.

The concomitant use of Zytram BID and sedative medicines, such as benzodiazepines or related medicines, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be fatal. Due to this, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes Zytram BID with sedative medicines, your doctor must limit the dose and duration of concomitant treatment.

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

These tablets must not be used with a monoamine oxidase inhibitor (MAOI), or if you have taken this type of medicine in the last 2 weeks (see section 2. "Do not take Zytram BID tablets").

The risk of side effects increases:

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

Tell 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;
• Medicines for depression;
• Medicines for treating psychiatric or mental illnesses;
• Ritonavir to treat HIV;
• Digoxin to treat heart failure or arrhythmias;
• Other potent painkillers (buprenorphine, nalbuphine, and pentazocine);
• Certain morphine-like medicines, for example, to treat cough or to treat withdrawal symptoms;
• 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 medicines to prevent blood clotting or to thin the blood (coumarin anticoagulants, such as warfarin);
• Ondansetron to treat nausea or general malaise.

Taking Zytram BID tablets with alcohol

Consult your doctor or pharmacist if you drink or intend to drink alcohol while being treated with this medicine.

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.

Pregnancy

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

Breastfeeding

Tramadol is excreted in breast milk. For this reason, you should not take Zytram BID more than once during breastfeeding, or if you take Zytram BID more than once, you should interrupt breastfeeding.

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

Driving and using machines

These tablets can cause a number of side effects, such as drowsiness, blurred vision, and dizziness, which may affect your ability to drive or use machines (see section 4 for a full list of side effects). These effects are more noticeable when you start treatment with the tablets or when the dose is increased. If you are affected, you should not drive or use machines.

Zytram BID tablets contain lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Zytram BID tablets

Follow exactly the administration instructions of these tablets given 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 BID, when and for how long you should take it, when to contact your doctor, and when to stop 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 of age

The usual initial dose is one 75 mg tablet twice a day. However, your doctor will prescribe the dose required to treat the pain you are experiencing. Do not exceed the dose recommended by your doctor. If you find that you still have pain while taking the tablets, consult your doctor. You should not take more than 400 mg per day.

Swallow the tablets with water. Do not crush, dissolve, or chew them.

The Zytram BID tablets are designed to provide adequate treatment over 12 hours when taken whole. If the tablet is broken, crushed, dissolved, or chewed, the full 12-hour dose may be absorbed quickly by your body, which can be dangerous and cause serious problems, such as a fatal overdose.

You should take the tablets every 12 hours. For example, if you took a tablet at 8 am, you should take the next tablet at 8 pm.

Elderly patients

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

Patients with liver or kidney impairment/patients on dialysis

If you have severe liver or kidney disease, treatment with Zytram BID 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 of age

The safety of Zytram BID in children between 1 and 12 years of age has not been established.

If you take more Zytram BID tablets than you should or someone takes your tablets accidentally

Contact your doctor or the nearest hospital immediately. People who have taken an overdose may experience excessive drowsiness, feel very unwell, or very dizzy. They may have 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 remaining tablets with you.

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

If you forget to take Zytram BID tablets

If you remember within the next 6 hours from the time you should have taken the tablet, take the missed tablet immediately. Then take the next tablet at the usual time. If more than 6 hours have passed, it is best to consult your doctor.

Do not take a double dose to make up for the missed dose.

If you stop taking Zytram BID tablets

Do not stop taking this medicine suddenly unless your doctor tells you to. If you want to stop taking your medicine, talk to your doctor first, especially if you have been taking it for a long time. Your doctor will tell you when and how to stop 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, you may experience withdrawal symptoms such as agitation, anxiety, nervousness, difficulty sleeping, unusual hyperactivity, tremors, or gastrointestinal disorders, e.g., upset stomach.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

All medicines can cause allergic reactions, even if 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 itching, especially if it affects the whole body.

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

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

Very Common:may affect more than 1 in 10 patients

• Dizziness (this effect usually subsides after a few days, however, your doctor may prescribe you some medication for dizziness if it continues to be a problem)
• Vertigo

Common:may affect up to 1 in 10 patients

• Somnolence (it is more frequent when starting to take the tablets or when the dose is increased, but it usually subsides after a few days)

• Dry mouth
• Sweating
• Vomiting (with a feeling of dizziness)

Uncommon:may affect up to 1 in 100 patients

• Headache
• Tachycardia, palpitations, or severe heart problems
• Feeling of "fainting" especially when standing up, low blood pressure (hypotension)
• Constipation
• Abdominal pain or discomfort
• Rash, hives (urticaria), or itching

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

• Tingling or numbness
• Blurred vision
• Hallucinations
• Nightmares
• Mood changes, feeling of discomfort and displeasure, or feeling of extreme happiness
• Changes in activity level
• Confusion
• Recognition problems, changes in thinking, memory, and behavior
• Seizures, tremors, or convulsions
• High blood pressure (hypertension)
• Shortness of breath, difficulty breathing, or wheezing
• Worsening of asthma
• Loss of appetite
• Diarrhea
• Pain or difficulty urinating
• Muscle weakness
• Redness of the skin
• Bradycardia
• Fainting

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

• Withdrawal symptoms when stopping the tablets, such as agitation, anxiety, nervousness, hyperactivity, tremors, difficulty sleeping, stomach upset
• Worsening of liver function tests (seen in blood tests)

Frequency Not Known:the frequency cannot be estimated from the available data

• Decrease in blood sugar levels
• Unusual feeling of weakness
• Withdrawal symptoms in babies born to mothers who have used tramadol during pregnancy (see section 2 "Pregnancy, breastfeeding, and fertility")
• Hiccup
• Need to take increasingly higher doses of the tablets to achieve the same level of pain relief (tolerance).
• Increased sensitivity to pain.
• Serotonin syndrome, which can manifest 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 stiffness, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "What you need to know before taking Zytram BID 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 Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Medicines Surveillance System for Human Use https://www.notificaram.es.

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

5. Conservation of Zytram BID Tablets

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

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

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

Do not store above 30°C.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Zytram BID Tablets

The active ingredient is tramadol hydrochloride. Each tablet contains 75 mg of tramadol hydrochloride.

The other components are:

• Hydrogenated vegetable oil
• Talc
• Magnesium stearate
• Lactose monohydrate
• Macrogol
• Hypromellose (E464)
• Titanium dioxide (E171)
• Iron oxide (E172)
• Carmine indigo (E132)

Appearance of the Product and Package Contents

This medicine is presented in the form of gray, round tablets, marked with "TBD" on one side and the dose (75) on the other side, with an approximate diameter of 7 mm.

Each carton contains 7, 14, 28, 30, 56, or 60 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Mundipharma Pharmaceuticals S.L.

Bahía de Pollensa, 11

28042 Madrid

Spain

Manufacturer

Mundipharma DC B.V.

Leusderend 16

3832 RC Leusden

Netherlands

or

ZAMBON SWITZERLAND LTD

Via Industria, 13 (Cadempino)

CH-6814 – Switzerland

Date of the Last Revision of this Prospectus:May 2024

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/