Prospecto: information for the user

Tramadol Krka 100 mg/2 ml injectable solution and for infusion EFG

tramadol, hydrochloride

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

-Keep this prospect, as you may have to read it again.

-If you have any doubts, consult your doctor or pharmacist.

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

1.What is Tramadol Krka and what it is used for

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

3.How to use Tramadol Krka

4.Possible adverse effects

5.Storage of Tramadol Krka

6.Contents of the package and additional information

Tramadol, the active ingredient ofthis medication, is an opioid analgesic that acts on the central nervous system. It relieves pain by acting on specific nerve cells in the spinal cord and brain.

Tramadol Krka is used for the treatment of moderate to severe pain.

No 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 alcohol, sleep aids, analgesics, or other psychotropic medications (medicines that affect mood and emotions) overdose.

•If you are also taking monoamine oxidase inhibitors (MAO), (a certain type of medication 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 epileptic and your seizures are not adequately controlled with treatment.

•As a substitute in drug withdrawal treatments.

Warnings and Precautions

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

•If you think you are addicted to other analgesics (opioids).

•If you have altered consciousness (think you are going to faint).

•If you are in shock (a sign of this state may be cold sweat).

•If you have high blood pressure in the skull (possibly after a head injury or brain diseases);

•If you have difficulty breathing;

•If you are prone to epilepsy or seizures;

•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 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 associated with this serious syndrome (see section 4 “Possible Adverse Effects”).

Respiratory Disturbances Related to Sleep

Tramadol may cause respiratory disturbances related to sleep such as central sleep apnea (pause in breathing during sleep) and sleep-related hypoxemia (low oxygen level in blood). These symptoms may be, 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.

Cases of 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 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 cause 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 to be used or the frequency with which it is used.

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 by a psychiatrist for other mental health conditions.

If you observe 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 discontinue the medication, and how to do it safely (see section 3, if you interrupt treatment with tramadol).

Inform your doctor, pharmacist, or nurse if you experience any of these problems while using this medication or if this information has been applied to you at any time.

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 if you should take a hormonal supplement.

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.

Children and Adolescents

This medication should not be administered to children under 1 year of age.

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 Tramadol Krka

Inform your doctor, pharmacist, or nurse if you are using, have used recently, or may need to use any other medication.

Tramadol Krka injectable and for infusion should not be used with monoamine oxidase inhibitors (MAO) (certain medications for treating depression) (see “Do not use Tramadol Krka”).

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

- carbamazepine (used to treat epilepsy)

- ondansetron (used to prevent nausea)

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

The risk of adverse effects increases:

• If you are using tramadol at the same time as medications that also have a depressant effect on brain function. You may feel dizzy or faint. If this happens, inform your doctor. Other medications include sedatives, sleep aids, and certain analgesics, such as morphine and codeine (also as an antitussive) and alcohol.
• If you are taking medications 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 indicate if tramadol is suitable for you.
• If you are taking certain antidepressants, tramadol may interact with these medications and you may experience a serotonin syndrome (see section 4 “Possible Adverse Effects”).

• If you are taking anticoagulant coumarins (medications that prevent normal blood coagulation), p. warfarin, with tramadol. The anticoagulant effect of these medications 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).

Use of 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, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

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

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

Generally, tramadol use during breastfeeding is not recommended. Small amounts of tramadol are excreted in breast milk. In a single dose, it is usually not necessary to discontinue breastfeeding. Ask your doctor, pharmacist, or nurse.

The experience of its use in humans 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 essential to observe how this medication 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 particularly careful at the start of treatment, after increasing the dose, after changing the formulation, and/or when taking it with other medications.

Tramadol Krka contains Sodium

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

Always use this medication exactly as your doctor has told you. Consult your doctor, pharmacist or nurse if you are unsure.

Before starting treatment and regularly during it, your doctor will also explain what you can expect from the use of 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 a daily dose of 8 ml of the medication (equivalent to 400 mg of tramadol hydrochloride), unless your doctor has explicitly prescribed it.

Unless your doctor tells you otherwise, the usual dose is:

Adults and adolescents 12 years and older

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

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

For doctors and healthcare professionals, you can find more information about the medication administration at the end of this prospectus.

Children

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

Children aged 1 to 11 years receive a single dose of 1 to 2 mg of tramadol hydrochloride per kilogram of body weight. In general, the lowest effective dose for analgesia should be selected. 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 about the medication administration in children at the end of this prospectus.

Older patients

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

Severe liver or kidney disease (insufficiency) / patients on dialysis

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

Administration form

How and when to use Tramadol Krka injectable solution and for infusion

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

Alternatively, the contents of the ampoule can be diluted and administered through infusion into a vein. For doctors and healthcare professionals, you can find more information about the medication administration at the end of this prospectus.

For how long to use Tramadol Krka injectable solution and for infusion

Do not use this medication for longer than necessary. If a prolonged treatment is considered necessary, your doctor will monitor you at regular short intervals (if necessary, with interruptions in treatment) to see if you should continue your treatment with tramadol and at what dose.

Talk to your doctor or pharmacist if you feel that the effect of this medication is too strong or too weak.

If you use more Tramadol Krka than you should

If you have taken an additional dose of tramadol, there are usually no negative effects. Use the next dose of this medication as prescribed.

If you have taken a significantly higher dose than recommended, the following may occur: pupil constriction, vomiting, decreased blood pressure, rapid heart rate, circulatory collapse, disturbances of consciousness up to coma (deep unconsciousness), 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 compensate for a missed dose, but continue as before.

If you interrupt treatment with Tramadol Krka

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

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

Generally, discontinuing 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 medication. They may feel restless, anxious, nervous or shaky. They may be hyperactive, have difficulty sleeping or experience gastrointestinal discomfort. Very few people experience panic attacks, hallucinations, false sensations, such as tingling, numbness and tingling, or ringing in the ears (tinnitus). Rarely, unusual symptoms of the central nervous system, such as confusion, delirium, altered perception of oneself (derealization) and reality (depersonalization) and paranoia, have been reported. If any of these side effects occur after discontinuing treatment with tramadol, contact your doctor.

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

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

Seek medical attention immediately if you experience symptoms of an allergic reaction, such as swelling of the face, tongue, and/or throat and/or difficulty swallowing or hives with difficulty breathing.

The most common side effects that occur during treatment withtramadol sare 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, drowsiness, fatigue, vomiting, constipation, dry mouth; excessive sweating (hyperhidrosis).

Rare: may affect up to 1 in 100 people

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

Cramps, gastrointestinal disorders (e.g., stomach pressure, 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, fluid retention in tissues [angioedema]) and anaphylactic reactions (sudden circulatory failure) occur very rarely.

Slow heart rate (bradycardia).

Increased blood pressure

Fake sensations in the skin (such as tingling, itching, numbness), tremors (tremors), epileptic seizures, involuntary muscle spasms, abnormal coordination, transient loss of consciousness (syncope), speech disorders.

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

Changes in appetite

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

Mental disorders may occur after treatment withtramadol; their intensity and nature may vary in individual patients (according to the patient's personality and treatment duration).

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

Drug dependence may occur.

Iftramadolis used for a prolonged period, there may be dependence, although the risk is low. After stopping treatment, withdrawal reactions may occur (see "If you stop taking Tramadol Krka").

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

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

If the recommended doses are exceeded or other medications that have a depressive effect on cerebral function are taken at the same time, breathing may slow down.

A worsening of asthma has been reported, but no causal relationship with the active ingredient tramadol could be established.

Decreased muscle strength (motor weakness).

Difficulty 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: the frequency cannot be estimated from the available data

Low blood sugar levels.

Hypotension.

Serotonin syndrome, which may manifest as changes in mental state (e.g., agitation, illusions, 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 Krka”).

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 Medicines for Human Use: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 and protected place, inaccessible to other people. This medication can cause severe and even fatal harm to individuals who have not been prescribed it.

Do not usethis medicationafter the expiration date appearing on the box and label after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

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

- sodium bicarbonate 4.2%

- Ringer's solution

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

- 0.9% sodium chloride,

- 0.18% sodium chloride and 4% glucose (dextrose),

- sodium lactate compound

- 5% glucose (dextrose)

From a microbiological standpoint, the medication should be used immediately. If not used immediately, storage times and conditions in use, prior to use, are the responsibility of the user.

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

Medications should not be disposed of through drains or trash. Dispose of containers and medications you no longer need at the SIGRE point of the pharmacy. Ask your pharmacist how to dispose of containers and medications you no longer need. This will help protect the environment.

Composition ofTramadolKrka

-The active ingredient is tramadol hydrochloride.

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

-The other components are anhydrous sodium acetate and water for injection preparations. See section 2 “Tramadol Krka contains sodium”.

AppearanceofTramadolKrkaand contents of the package

Theinjectable and infusion solutionis transparent, colorless and practically free of particles.

Available in boxes of 1, 5, 10, 20, 25, and 100 ampoules (packaged in blisters) of 2 ml of injectable and infusion 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

Responsible for manufacturing

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

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

Further information about this medicinal product can be obtained by contacting the local representative of the marketing authorization holder:

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

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

Last update of thissummary of product characteristics: July 2024

This information is intended solely for medical professionals or healthcare professionals:

Tramadol Krka 100 mg/2 ml solución inyectable y para perfusión EFG

Tramadol hydrochloride

Note on opening the easily breakable ampoule

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

1. Turn the ampoule until the breaking point is facing upwards.

2. Break the top of the ampoule.

Further information on administration

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

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

The injectable and infusion solution is injected intravenously, intramuscularly or subcutaneously (intravenouslyTramadol Krka is injectedusually in a superficial vein of the arm, intramuscularly mainly in the gluteal muscle and subcutaneously under the skin).

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

Alternatively,the medicinal productcan be diluted with an appropriate infusion 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 infusion or patient-controlled analgesia (PCA).

Incompatibilities

This medicinal product should not be mixed with other medicinal products, except those mentioned in this section (Further information on administration).

How to useTramadol Krka solución inyectable y para perfusiónfor the 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).

2) Calculation of thevolume of the diluted solution of tramadol hydrochloride for injection/infusion to be injected: ??divide the total dose (mg) by an appropriate concentration of the diluted solution for injection/infusion (mg/ml, see the table below).

For this,Tramadol Krkais diluted with water for injection preparations. The following summary shows the concentrations achieved (1 ml ofTramadol Krkacontains 50 mg of tramadol hydrochloride):

Dilution ofTramadol Krka 100 mg/2 ml solución inyectable y para perfusión:

Example: We want to administer a dose of 1.5 mg of tramadol hydrochloride per kilogram of body weight to a child weighing 45 kg.To do this, 67.5 mg of tramadol hydrochloride are required.Dilute 2 ml ofTramadol Krka 100 mg/2 ml solución inyectable y para perfusión(equivalent to one ampoule of 2 ml) with 4 ml ofwater for injections.This gives a concentration of 16.7 mg of tramadol hydrochloride per milliliter.From the diluted solution, 4 ml (approximately 67 mg of tramadol hydrochloride) are administered.