Tramadol Krka 100 mg/2 ml solution for injection and infusion EFG: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Tramadol Krka 100 mg/2 ml injection solution and infusion solution EFG

tramadol, hydrochloride

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, consult your doctor or pharmacist.
If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet Contents

What Tramadol Krka is and what it is used for
What you need to know before using Tramadol Krka
How to use Tramadol Krka
Possible side effects
How to store Tramadol Krka
Contents of the pack and other information

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

Tramadol, the active substance in this medicine, is an opioid-type 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 to treat moderate to severe pain.

2. What you need to know before using Tramadol Krka

Do not use Tramadol Krka

if you are allergic to tramadol or to any of the other components of this medicine (listed in section 6).
if you have had acute intoxication with alcohol, sleeping medications, painkillers, or other psychotropic medicines (medicines that affect mood and emotions).
if you are also taking monoamine oxidase inhibitors (MAOIs) (a certain type of medicine used to treat depression), or if you have taken them within the last 2 weeks (see “Other medicines and Tramadol Krka”).
if you have epilepsy and your seizures are not adequately controlled by treatment.
as a substitute in drug withdrawal treatments.

Warnings and precautions

Consult your doctor or nurse before starting treatment with Tramadol Krka injectable solution and for infusion:

if you think you are addicted to other painkillers (opioids).
if you have disturbances in consciousness (feel as though you might faint).
if you are in shock (a sign of shock may be cold sweating).
if you have increased pressure inside the skull (possibly after 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 low risk that you may experience serotonin syndrome after taking tramadol, particularly when used in combination with certain antidepressants, or even with tramadol alone. Contact a doctor immediately if you develop any symptoms associated with this serious condition (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 blood oxygen levels during sleep). Symptoms may include pauses in breathing during sleep, waking up at night due to difficulty breathing, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, consult your doctor. Your doctor may consider reducing the dose.

Seizures have been reported 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 may result in reduced effectiveness of the medicine (the body becomes accustomed to it, known as pharmacological tolerance). Repeated use of tramadol may also lead to dependence, abuse, and addiction, which could potentially result in fatal overdose. The risk of these adverse effects may be higher with higher doses and prolonged use.

Dependence or addiction may lead to a feeling of loss of control over how much medicine you take or how often you take it.

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

You or a family member have abused or been dependent on alcohol, prescription medicines, or illegal drugs (“addiction”).
You are a smoker.
You have previously had mood disorders (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, they could be signs of dependence or addiction:

You need to use the medicine for longer than prescribed by your doctor.
You need to take 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 taking the medicine, and feel better once you take it again (“withdrawal effects”).

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

Inform your doctor, pharmacist, or nurse if you experience any of these problems while using this medicine, or if any of this information applies to you.

Extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These symptoms may indicate adrenal insufficiency (low cortisol levels). If you experience any of these symptoms, inform your doctor, who will decide whether you need hormonal supplementation.

Tramadol is metabolized in the liver by an enzyme. Some people have a variation of this enzyme, which may affect individuals differently. In some people, adequate pain relief may not be achieved, while others may be more likely to experience serious adverse effects. If you notice any of the following adverse effects, 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

This medicine must not be given 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 symptoms of tramadol toxicity may worsen in these children.

Other medicines and Tramadol Krka

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines.

Tramadol Krka injectable solution and for infusion must not be used together with MAO inhibitors (certain medicines used to treat depression) (see “Do not use Tramadol Krka”).

The analgesic effect of tramadol may be weakened and/or shortened if you are also taking medicines containing any of the following active substances:

carbamazepine (used to treat epilepsy)
ondansetron (used to prevent nausea)

Your doctor will advise you whether you can use tramadol and what dose you should take.

The risk of adverse 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 occurs, inform your doctor. These other medicines include sedatives, sleeping medicines, and certain painkillers such as morphine and codeine (also used as cough suppressants), and alcohol.
if you are taking medicines that may cause seizures (fits), 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 advise you whether 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 coumarin anticoagulants (medicines that prevent normal blood clotting), e.g., warfarin, together with tramadol. The anticoagulant effect of these medicines may be affected, leading to bleeding.
if you are taking gabapentin or pregabalin to treat epilepsy or nerve-related pain (neuropathic pain).

Use of Tramadol Krka with food, drinks, and alcohol

Do not consume alcohol during treatment with tramadol, as its effects may be intensified. Food does not affect the action 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 limited 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 fetal dependence on tramadol and, consequently, withdrawal symptoms in the newborn after birth.

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

Experience from human use suggests that tramadol has no effect on male or female fertility.

Driving and using machines

Ask your doctor whether you can drive or use machines during treatment with tramadol. It is important to observe how this medicine affects you before driving or operating machinery. Do not drive or use machines if you feel drowsy, dizzy, have blurred or double vision, or have difficulty concentrating. Exercise particular caution at the beginning of treatment, after a dose increase, after a change in formulation, and/or when used together with other medicines.

Tramadol Krka contains sodium

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

3. How to use Tramadol Krka

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist, or nurse if you are unsure.

Before starting treatment and regularly during treatment, your doctor will also explain to you 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 according to the intensity of your pain and your individual sensitivity. In general, the lowest effective dose needed to relieve pain should be taken. The daily dose of 8 ml of the medicine (equivalent to 400 mg of tramadol hydrochloride) must not be exceeded unless explicitly prescribed by your doctor.

Unless otherwise directed by your doctor, the usual dose is:

Adults and adolescents aged 12 years and older

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

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

For doctors and healthcare professionals, further information on the administration of the medicine can be found at the end of this leaflet.

Children

This medicine 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. Generally, the lowest effective dose for analgesia should be selected. The daily dose must not exceed 8 mg per kg of body weight or 400 mg, whichever is lower.

For doctors and healthcare professionals, further information on the administration of the medicine in children can be found at the end of this leaflet.

Elderly patients

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

Severe liver or kidney disease (impairment) / dialysis patients

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

Method of administration

How and when to use Tramadol Krka injectable and infusion solution

This medicine is administered by intravenous, intramuscular, or subcutaneous injection (intravenously, the injectable and infusion solution is usually 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 may be diluted and administered into a vein by infusion. For doctors and healthcare professionals, further information on the administration of the medicine can be found at the end of this leaflet.

For how long to use Tramadol Krka injectable and infusion solution

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

Talk to your doctor or pharmacist if you feel that the effect of this medicine 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 will generally be no negative effects. Take the next dose of this medicine as prescribed.

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

If you forget to use Tramadol Krka

If you accidentally forget to take the tramadol solution, your pain may return. Do not take a double dose to make up for a missed dose, but continue as before.

If you stop treatment with Tramadol Krka

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

If you wish to discontinue treatment due to unpleasant side effects, speak with your doctor.

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences 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 hives with difficulty breathing.

The most common adverse effects occurring during treatment with tramadol are nausea and dizziness, which occur in more than 1 in every 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.

Nausea, gastrointestinal disorders (e.g., stomach pressure, bloating), diarrhoea.

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

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

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

Slow heartbeat (bradycardia).

Increased blood pressure.

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

Epileptic seizures occurred mainly after use of high doses of tramadol or after concomitant use of medicines that may trigger seizures.

Changes in appetite.

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

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

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

Drug dependence may occur.

If tramadol is used for a prolonged period, dependence may develop, although the risk is low. After discontinuation of treatment, withdrawal reactions may occur (see "If you stop taking Tramadol Krka").

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

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

If recommended doses are exceeded or if other medicines with a depressant effect on brain function are administered simultaneously, breathing may be slowed.

Worsening of asthma has been reported, but a causal relationship with the active substance tramadol could not be established.

Decreased muscle strength (motor weakness).

Difficulty or pain when urinating, 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.

Hiccups.

Serotonin syndrome, which may present with 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 rigidity, lack of coordination and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea) (see section 2 "What you need to know before taking Tramadol Krka").

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Tramadol Krka

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

Store this medicine in a safe and secure place, inaccessible to others. This medicine may cause serious harm or even be fatal to individuals for whom it has not been prescribed.

Do not use this medicine after the expiry date stated on the carton and label after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

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

Sodium bicarbonate 4.2%
Ringer's solution

Chemical and physical in-use stability has been demonstrated for 5 days at 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 medicine should be used immediately. If not used immediately, the responsibility for storage conditions and duration of in-use storage prior to use lies with the user.

Do not use this medicine if you notice that the solution is not clear and free from particles, or if the container is damaged.

Medicines must not be disposed of via wastewater or household waste. Return unused medicines and their containers to the SIGRE point at your pharmacy. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Package contents and other information

Composition of Tramadol Krka

The active substance is tramadol hydrochloride.

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

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

Appearance of Tramadol Krka and contents of the pack

The injectable and infusion solution is clear, colourless and practically free from particles.

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

Only some pack 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

For further information about this medicinal product, please contact 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 European Economic Area member states under the following names:

Member State	Medicinal Product Name
Croatia	Awardix 100 mg otopina za injekciju/infuziju
Czech Republic	Tramadol Krka
Belgium	Tramadol Krka 100 mg/2ml oplossing voor injectie/infusie
Bulgaria	???????? ???? 100 mg/2ml ???????????/?????????? ???????
Hungary	Tramadol Krka 100 mg/2 ml oldatos injekció vagy infúzió
Germany	Tramadol TAD 100 mg Injektions-/Infusionslösung
Spain	Tramadol Krka 100 mg/2 ml solución inyectable y para perfusión EFG
Poland	Tramadol Krka
Slovakia	Tramadol Krka 100mg/2ml injekcný/ infúzny roztok

Date of the most recent review of this leaflet: July 2024

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

This information is intended for healthcare professionals only:

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

Tramadol hydrochloride

Note on opening the easy-break ampoule

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

Rotate the ampoule until the break point is facing upwards.
Snap off the top part of the ampoule.

Further 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 required for on-demand analgesia (pain treatment as needed) during the early postoperative period. Requirements over a 24-hour period are generally no higher than with conventional administration.

The solution for injection and infusion is administered intravenously, intramuscularly, or subcutaneously (intravenously, Tramadol Krka is usually injected into a superficial vein in the arm; intramuscularly, mainly into the gluteal muscle; and subcutaneously, under the skin).

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

Alternatively, the medicine may 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 solution, glucose 5%) and used for intravenous infusion or patient-controlled analgesia (PCA).

Incompatibilities

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

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

Calculation of injection volume

Calculation of the required dose of tramadol hydrochloride in mg: body weight (kg) × dose (mg/kg).
Calculation of the volume of diluted tramadol hydrochloride solution for injection/infusion to be administered: ??divide the total dose (mg) by an appropriate concentration of the diluted injection/infusion solution (mg/ml; see table below).

For this purpose, Tramadol Krka is diluted with water for injections. The following summary shows the resulting concentrations (1 ml of Tramadol Krka contains 50 mg of tramadol hydrochloride):

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

With water for injections	Yields the following concentrations
Tramadol Krka 100 mg/2 ml injection and infusion solution
2 ml + 2 ml	25.0 mg/ml
2 ml + 4 ml	16.7 mg/ml
2 ml + 6 ml	12.5 mg/ml
2 ml + 8 ml	10.0 mg/ml
2 ml + 10 ml	8.3 mg/ml
2 ml + 12 ml	7.1 mg/ml
2 ml + 14 ml	6.3 mg/ml
2 ml + 16 ml	5.6 mg/ml
2 ml + 18 ml	5.0 mg/ml

Example: We wish to administer a dose of 1.5 mg of tramadol hydrochloride per kilogram of body weight to a child weighing 45 kg. For this, 67.5 mg of tramadol hydrochloride is required. Dilute 2 ml of Tramadol Krka 100 mg/2 ml concentrate for solution for injection and infusion (equivalent to one 2 ml ampoule) with 4 ml of water for injections. This yields a concentration of 16.7 mg of tramadol hydrochloride per millilitre. From the diluted solution, administer 4 ml (approximately 67 mg of tramadol hydrochloride).