TRAMADOL KRKA 100 mg/2 ml Injectable Solution and Perfusion Solution

2. What you need to know before you use Tramadol Krka

Do not useTramadolKrka

• if you are allergic to tramadol or any of the other ingredients of this medicine (listed in section 6).
• if you have had an acute overdose of alcohol, sleeping pills, pain relievers, or other psychoactive medicines (medicines that affect mood and emotions)
• if you are also taking monoamine oxidase inhibitors (MAOIs), (a certain type of medicine for the treatment of depression), or if you have taken them in the last 2 weeks (see “Other medicines and Tramadol Krka”).
• if you are an epileptic and your seizures are not adequately controlled with treatment.
• as a substitute in treatments for drug withdrawal.

Warnings and precautions

Consult your doctor or nurse before starting to use Tramadol Krka solution for injection and infusion:

• if you think you are addicted to other pain relievers (opioids).
• if you have altered consciousness (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 high pressure in the skull (possibly after a head injury or brain diseases);
• if you have difficulty breathing;
• if you are prone to suffering from epilepsy or convulsions;
• if you have liver or kidney problems;
  • if you suffer from depression and are taking antidepressants as some may interact with tramadol (see “Other medicines and Tramadol Krka”).

Serotonin syndrome

There is a slight risk that you may experience serotonin syndrome, which may occur after taking tramadol in combination with certain antidepressants or tramadol monotherapy. Consult a doctor immediately if you experience any of the symptoms associated with this serious syndrome (see section 4 “Possible side effects”).

Sleep-related breathing disorders

Tramadol may cause sleep-related breathing disorders such as central sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen level in the blood). These symptoms may be pauses in breathing during sleep, nocturnal awakening 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.

Seizures have been described in patients using tramadol at the recommended dose. The risk may increase when the maximum recommended daily dose of 400 mg of tramadol is exceeded.

Tolerance, dependence, and addiction

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

Dependence or addiction can cause a feeling of lack of control over the amount of medicine you need to use or how often you need to use it.

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

• You or any member of your family have abused alcohol or experienced dependence on it, prescription medicines, or illegal drugs (“addiction”).
• You are a smoker.
• You have 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 symptoms while using tramadol, it could be a sign of dependence or addiction:

• You need to use the medicine for a longer period than indicated by your doctor.
• You need to use a higher dose than recommended.
• You are using the medicine for reasons other than those prescribed, for example, “to feel calm” or “to help you sleep”.

• You have made repeated, unsuccessful attempts to stop using the medicine or control its use.
• You feel unwell when you stop using the medicine, and you feel better once you take it again (“withdrawal effects”).

If you notice any of these signs, consult your doctor to determine the best treatment option for you, when it is appropriate to stop the medicine, and how to do it safely (see section 3, if you stop treatment with tramadol).

Inform your doctor, pharmacist, or nurse if you have any of these problems while using this medicine or if this information has ever applied to you.

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, he will decide if you should 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.

Children and adolescents

The medicine must not be administered to children under 1 year of age.

Use in children with respiratory problems

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

Other medicines and Tramadol Krka

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicines.

Tramadol Krka solution for injection and infusion must not be used together with MAOIs (certain medicines for treating depression) (see "Do not use Tramadol Krka").

The analgesic effect of tramadol may be weakened and/or shortened if you also take medicines that contain one of the following active substances:

• carbamazepine (used to treat epilepsy)
• ondansetron (used to prevent feeling sick)

Your doctor will tell you if you can use tramadol and what dose you should use.

The risk of side effects increases:

• if you are using tramadol at the same time as medicines that also have a depressant effect on brain function. You may feel dizzy or faint. If this happens, inform your doctor. Other medicines include sedatives, sleeping pills, and certain pain relievers, such as morphine and codeine (also as a cough suppressant) and alcohol.
• if you are taking medicines that can cause seizures (attacks), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take tramadol at the same time. Your doctor will tell you if tramadol is suitable for you.
• if you are taking certain antidepressants, tramadol may interact with these medicines, and you may experience serotonin syndrome (see section 4 “Possible side effects”).

• if you are taking anticoagulant coumarins (medicines that prevent normal blood clotting), e.g., warfarin, together with tramadol. The anticoagulant effect of these medicines may be affected, and there may be bleeding.
• if you are taking gabapentin or pregabalin to treat epilepsy or pain due to nerve problems (neuropathic pain).

Using Tramadol Krka with food, drinks, and alcohol

Do not consume alcohol during tramadol treatment, as its effects may be intensified. Food does not affect the effect of tramadol.

Pregnancy and breastfeeding

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

There is very little information on the safety of tramadol during pregnancy. Therefore, you should not use tramadol if you are pregnant.

Chronic use of tramadol during pregnancy may lead to the habituation of the fetus to tramadol and, consequently, to withdrawal symptoms after birth in the newborn.

In general, the use of tramadol is not recommended during breastfeeding. Very small amounts of tramadol are excreted in breast milk. With a single dose, it is generally not necessary to interrupt breastfeeding. Ask your doctor, pharmacist, or nurse.

Human experience suggests that tramadol has no effect on male and female fertility.

Driving and using machines

Ask your doctor if you can drive or use machines during tramadol treatment. 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 sleepy, 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 together with other medicines.

Tramadol Krka contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per unit volume; this is, essentially “sodium-free”.

3. How to use Tramadol Krka

Always use this medicine exactly as your doctor has told you. Consult your doctor, pharmacist, or nurse if you are not sure.

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

The dose should be adjusted to the intensity of your pain and your individual sensitivity. In general, the lowest dose should be taken to relieve pain. Do not exceed the daily dose of 8 ml of the medicine (equivalent to 400 mg of tramadol hydrochloride), unless your doctor has explicitly prescribed it.

Unless the doctor indicates otherwise, the usual dose is:

Adults and adolescents from 12 years

Depending on the pain, 1 to 2 ml of tramadol solution for injection is administered (equivalent to 50-100 mg of tramadol hydrochloride).

Depending on the pain, the effect lasts from 4 to 6 hours.

For doctors and healthcare professionals, you can find more information on the administration of the medicine at the end of this leaflet.

Children

This medicine is not indicated for use in children under 1 year of age.

Children from 1 to 11 years of age receive a single dose of 1 to 2 mg of tramadol hydrochloride per kilogram of body weight. In general, the lowest effective dose should be selected for analgesia. Do not exceed a daily dose of 8 mg per kg of body weight or 400 mg. The lower of the two doses should be administered.

For doctors and healthcare professionals, you can find more information on the administration of the medicine in children at the end of this leaflet.

Elderly patients

In elderly patients (over 75 years), the excretion of tramadol may be delayed. If this applies to you, your doctor may recommend prolonging the dosing interval.

Severe liver or kidney disease (insufficiency) / dialysis patients

Patients with severe liver and/or kidney insufficiency must not use this medicine. If in your case the insufficiency is mild or moderate, your doctor may recommend prolonging the dosing interval.

Method of administration

How and when to useTramadol Krka solution for injection and infusion

This medicine is injected intravenously, intramuscularly, or subcutaneously (intravenously, the solution for injection and infusion is generally injected into a superficial vein in the arm, intramuscularly mainly into the gluteal muscle, and subcutaneously under the skin).

Alternatively, the contents of the ampoule can be diluted and administered into a vein by infusion. For doctors and healthcare professionals, you can find more information on the administration of the medicine at the end of this leaflet.

For how long to useTramadol Krka solution for injection and infusion

Do not use this medicine for longer than necessary. If prolonged treatment is considered necessary, your doctor will regularly check, at short intervals (if necessary, by interrupting treatment), whether you should continue your treatment with tramadol and at what dose.

Talk to your doctor or pharmacist if you think the effect of this medicine is too strong or too weak.

If you use more Tramadol Krka than you should

If you have used an additional dose of tramadol, generally, there will be no negative effects. Use the next dose of this medicine as prescribed.

If you have used a significantly higher dose than recommended, the following may occur: constricted pupils, vomiting, decreased blood pressure, rapid heartbeat, circulatory collapse, disorders of consciousness up to coma (deep unconsciousness), epileptic seizures, and difficulty breathing up to respiratory arrest. If these signs appear, contact your doctor immediately.

If you forget to use Tramadol Krka

If you forget to use the tramadol solution by mistake, your pain may return. Do not use a double dose to make up for a forgotten dose, but continue as before.

If you stop treatment with Tramadol Krka

If you stop or prematurely end treatment with tramadol, it is likely that your pain will return.

If you want to stop treatment because you have unpleasant side effects, talk to your doctor.

In general, stopping treatment with tramadol does not cause any side effects. However, side effects may occur in some patients who have been using tramadol for a long time and suddenly stop using the medicine. They may feel restless, anxious, nervous, or trembly. They may be overactive, have difficulty sleeping, or have gastrointestinal problems. Very few people experience panic attacks, hallucinations, false sensations, such as tingling, numbness, or tingling, or ringing in the ears (tinnitus). Very rare, unusual symptoms of the central nervous system have been reported, such as confusion, delusional ideas, altered perception of oneself (depersonalization) and reality (derealization), and paranoia. If any of these side effects occur after stopping treatment with tramadol, contact your doctor.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

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

Contact a doctor immediately if you experience symptoms of an allergic reaction, such as swelling of the face, tongue, and/or throat, and/or difficulty swallowing or urticaria with difficulty breathing.

The most frequent adverse effects that occur during treatment with tramadol are nausea and dizziness, which occur in more than 1 in 10 users.

Very Common: may affect more than 1 in 10 people

Dizziness, nausea.

Common: may affect up to 1 in 10 people

Headache, somnolence, fatigue, vomiting, constipation, dry mouth; excessive sweating (hyperhidrosis).

Uncommon: may affect up to 1 in 100 people

Effects on cardiovascular regulation (palpitations, increased heart rate [tachycardia], dizziness [postural hypotension] or circulatory collapse). These adverse effects may occur especially when standing and in patients who are physically stressed.

Gagging, gastrointestinal disorders (e.g., pressure on the stomach, bloating), diarrhea.

Skin reactions (e.g., itching, rash).

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

Allergic reactions (e.g., difficulty breathing [dyspnea], wheezing, water retention in tissues [angioedema]) and shock reactions (sudden circulatory failure) occur very rarely.

Slow heartbeat (bradycardia).

Increased blood pressure

False sensations in the skin (such as tingling, itching, numbness), tremors (shaking), epileptiform convulsions, involuntary muscle spasms, abnormal coordination, transient loss of consciousness (syncope), speech disorders.

Epileptic seizures occurred mainly after the use of high doses of tramadol or after concomitant use of medications that can trigger seizures.

Changes in appetite

Hallucinations, confusion, sleep disorders, delirium, anxiety, and nightmares.

Mental disorders may occur after treatment with tramadol; their intensity and nature may vary in individual patients (depending on the patient's personality and treatment duration).

These include changes in mood (generally euphoric mood, occasionally irritated mood), changes in activity (generally suppression, occasionally increased) and decreased sensory perception and cognition, which can lead to errors in decision-making (reduction in sensory and cognitive performance).

Drug dependence can occur.

If tramadol is used for a longer period, dependence may occur, although the risk is low. After discontinuing treatment, withdrawal reactions may occur (see "If you stop treatment with Tramadol Krka").

Blurred vision, pupil constriction (miosis), extremely dilated pupils (mydriasis).

Slow breathing (respiratory depression), difficulty breathing (dyspnea).

If the recommended doses are exceeded or if other medications with a depressant effect on brain function are administered at the same time, breathing may slow down.

A worsening of asthma has been reported, but a causal relationship with the active ingredient tramadol could not be established.

Decreased muscle strength (motor weakness).

Difficult or painful urination, less urine than normal (urinary disorders and dysuria).

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

Elevated liver enzymes.

Unknown: frequency cannot be estimated from available data

Low 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 Krka").

Reporting 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 does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Tramadol Krka

Keep this medicine out of sight and reach of children.

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

Do not use this medicine after the expiration date shown on the box and label after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

The chemical and physical stability in use has been demonstrated for 24 hours up to 25 °C with the following perfusion solutions:

• sodium bicarbonate 4.2%
• Ringer's solution

The chemical and physical stability in use has been demonstrated for 5 days up to 25 °C with the following perfusion solutions:

• 0.9% sodium chloride,
• 0.18% sodium chloride and 4% glucose (dextrose),
• sodium lactate compound
• 5% glucose (dextrose)

From a microbiological point of view, the medicine should be used immediately. If not used immediately, the storage times and conditions in use, before use, are the responsibility of the user.

Do not use this medicine if you notice that the solution is not transparent and free of particles or if the container is damaged.

Medicines should not be thrown away through drains or into 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. Package Contents and Additional Information

Composition of Tramadol Krka

• The active ingredient is tramadol hydrochloride.

2 ml of injectable and perfusion solution (1 ampoule) contains 100 mg of tramadol hydrochloride. 1 ml of injectable and perfusion solution contains 50 mg of tramadol hydrochloride.

• The other components are sodium acetate anhydrous and water for injectable preparations. See section 2 "Tramadol Krka contains sodium".

Appearance of Tramadol Krka and Package Contents

The injectable and perfusion solution is transparent, colorless, and practically free of particles.

Available boxes of 1, 5, 10, 20, 25, and 100 ampoules (packaged in blisters) of 2 ml of injectable and perfusion solution. The ampoules are marked with a red dot and a green ring.

Only some package sizes may be marketed.

Marketing Authorization Holder

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L., Calle de Anabel Segura, 10, 28108 Alcobendas, Madrid, Spain

This medicine is authorized in the member states of the European Economic Area under the following names:

Date of the last revision of this prospectus: July 2024

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

This information is intended only for doctors or healthcare professionals:

Tramadol Krka 100 mg/2 ml solution for injection and perfusion EFG

Tramadol hydrochloride

Note on the easy-to-break ampoule opening

The ampoule has a breaking point and can be easily opened without tools.

1. Turn the ampoule until the breaking point is facing up.
2. Break the top of the ampoule.

More information on administration

If the pain is acute, administer a single dose of 2 ml of Tramadol Krka (equivalent to 100 mg of tramadol hydrochloride).

For the treatment of acute postoperative pain, even higher doses may be necessary for analgesia on demand (pain treatment as needed) in the early postoperative period. The requirements during a 24-hour period are generally not higher than during conventional administration.

The injectable and perfusion solution is injected intravenously, intramuscularly, or subcutaneously (intravenously, Tramadol Krka is usually injected into a superficial blood vessel of the arm, intramuscularly mainly into the gluteal muscle, and subcutaneously under the skin)

Intravenous administration is slow, i.e., 1 ml of injectable solution (equivalent to 50 mg of tramadol hydrochloride) per minute.

Alternatively, the medicine can be diluted with a suitable perfusion solution (e.g., sodium bicarbonate 4.2%, Ringer's solution, sodium chloride 0.9%, sodium chloride 0.18% and glucose 4%, sodium lactate compound, glucose 5%) and used for intravenous perfusion or patient-controlled analgesia (PCA).

Incompatibilities

This medicine should not be mixed with other medicines, except those mentioned in this section (Additional information on administration).

How to use Tramadol Krka solution for injection and perfusion for treatment in children over 1 year of age (see "How to use Tramadol Krka")

Calculation of the injection volume

1. Calculation of the required dose of tramadol hydrochloride in mg: body weight (kg) x dose (mg/kg).

1. Calculation of the volume of the diluted tramadol hydrochloride solution for injection/perfusion to be injected: divide the total dose (mg) by a suitable concentration of the diluted solution for injection/perfusion (mg/ml, see the table below).

To do this, Tramadol Krka is diluted with water for injectable preparations. The following summary shows the achieved concentrations (1 ml of Tramadol Krka contains 50 mg of tramadol hydrochloride):

Dilution of Tramadol Krka 100 mg/2 ml solution for injection and perfusion:

Example: We want to administer a dose of 1.5 mg of tramadol hydrochloride per kilogram of body weight to a child who weighs 45 kg. To do this, 67.5 mg of tramadol hydrochloride is needed. Dilute 2 ml of Tramadol Krka 100 mg/2 ml solution for injection and perfusion (equivalent to a 2 ml ampoule) with 4 ml of water for injection. This yields a concentration of 16.7 mg of tramadol hydrochloride per milliliter. From the diluted solution, administer 4 ml (approximately 67 mg of tramadol hydrochloride).