Tramadol Krka

Leaflet attached to the packaging: patient information

Tramadol Krka 50 mg/mL solution for injection/infusion

Tramadol Krka 100 mg/2 mL solution for injection/infusion

Tramadol hydrochloride

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Tramadol Krka and what is it used for
• 2. Important information before using Tramadol Krka
• 3. How to use Tramadol Krka
• 4. Possible side effects
• 5. How to store Tramadol Krka
• 6. Contents of the packaging and other information

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

Tramadol, the active substance of Tramadol Krka solution for injection/infusion, is a pain-relieving medicine belonging to the class of opioids acting on the central nervous system. It relieves pain by acting on certain nerve cells in the spinal cord and brain. Tramadol Krka solution for injection/infusion is used to treat moderate to severe pain.

2. Important information before using Tramadol Krka

When not to use Tramadol Krka

• in case of acute alcohol intoxication, sleeping pills, painkillers, or other psychotropic drugs (drugs that affect mood and emotions);
• as a substitute therapy for opioid dependence.

Warnings and precautions

Before starting to use Tramadol Krka solution for injection/infusion, the patient should inform their doctor or pharmacist:

Serotonin syndrome After taking tramadol in combination with certain antidepressants or tramadol alone, there is a small risk of so-called serotonin syndrome. If the patient experiences any symptoms of this syndrome with a severe course, they should immediately consult a doctor (see section 4 "Possible side effects"). Sleep apnea Tramadol Krka may cause sleep apnea, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, nighttime awakenings due to shortness of breath, difficulty maintaining sleep, or excessive daytime sleepiness. If the patient or another person observes these symptoms, they should contact a doctor. The doctor may recommend reducing the dose. There have been reports of seizures in patients taking tramadol at the recommended dose. This risk may be increased if the recommended maximum daily dose of tramadol of 400 mg is exceeded. Tolerance, dependence, and addiction This medicine contains tramadol, which is an opioid medicine. Repeated use of opioids can lead to reduced efficacy of the medicine (the patient's body gets used to the medicine, which is called tolerance). Repeated use of Tramadol Krka may also lead to dependence, abuse, and addiction, which can cause life-threatening overdose. The risk of these side effects may increase with the dose and duration of use of the medicine. Dependence or addiction can cause the patient to lose control over the amount of medicine taken or the frequency of its use. The risk of dependence on Tramadol Krka may be higher in people in the following situations:

If the patient notices any of the following symptoms while taking Tramadol Krka, it may indicate dependence or addiction.

• Need to take the medicine for a longer period than recommended by the doctor.
• Need to take a higher dose than recommended.
• The patient uses the medicine for reasons other than those for which it was prescribed, such as "to calm down" or "to sleep better".
• The patient has made repeated, unsuccessful attempts to stop or control the use of the medicine.
• After stopping the medicine, the patient feels unwell, and after taking it again, they feel better ("withdrawal symptoms").

If the patient notices any of these symptoms, they should consult a doctor to discuss the best treatment option, including when to stop taking the medicine and how to do it safely (see section 3, Stopping Tramadol Krka). If any of these problems occur during treatment with Tramadol Krka solution for injection/infusion or have occurred in the past, the patient should inform their doctor, pharmacist, or nurse. The patient should contact their doctor if they experience any of the following symptoms while taking Tramadol Krka: Excessive fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. This may indicate that the patient has adrenal insufficiency (low cortisol levels). If such symptoms occur, the patient should contact their doctor, who will decide whether the patient needs hormone replacement. Tramadol is converted in the liver by an enzyme. In some people, there is a certain variation of this enzyme, which can have different effects. In some people, pain relief may not be sufficient, and in others, the risk of severe side effects may be higher. The patient should stop using the medicine and immediately contact their doctor if they experience any of the following side effects: slowed breathing or shallow breathing, confusion, drowsiness, pupil constriction, nausea, or vomiting, constipation, loss of appetite.

Children and adolescents

The medicine should not be given to children under 1 year of age. Use in children with breathing disorders It is not recommended to use tramadol in children with breathing disorders, as the symptoms of tramadol toxicity may be exacerbated.

Tramadol Krka and other medicines

The patient should inform their doctor, pharmacist, or nurse about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. Tramadol Krka solution for injection/infusion should not be used at the same time as MAO inhibitors (certain medicines used to treat depression) (see "When not to use Tramadol Krka"). The pain-relieving effect of Tramadol Krka solution for injection/infusion may be weakened and/or its duration may be shortened when taken with medicines containing:

• carbamazepine (used to treat seizures),
• ondansetron (an antiemetic medicine).

The doctor will decide whether the patient can take Tramadol Krka solution for injection/infusion and in what dose. Concomitant use of Tramadol Krka and sedative medicines, such as benzodiazepines or similar medicines, increases the risk of drowsiness, breathing difficulties (respiratory failure), coma, and can be life-threatening. Therefore, concomitant use of these medicines can only be considered when other treatment options are not possible. However, if the doctor prescribes Tramadol Krka with sedative medicines, they should limit the dose and duration of concomitant use. The patient should inform their doctor about all sedative medicines they are taking and strictly follow the dosage recommendations. It may be helpful to inform friends or family members to be aware of these symptoms. If such symptoms occur, the patient should contact their doctor. The risk of side effects increases:

• when using Tramadol Krka solution for injection/infusion with medicines that have a depressant effect on brain function. Dizziness and fainting may occur. In such cases, the patient should consult their doctor. Other medicines include sleeping pills and certain painkillers, such as morphine and codeine (which also has an antitussive effect), as well as alcohol.

Tramadol Krka with food, drink, and alcohol

The patient should not drink alcohol while being treated with Tramadol Krka solution for injection/infusion, as it may enhance its effect. Food does not affect the effect of Tramadol Krka solution for injection/infusion.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor, pharmacist, or nurse before using this medicine. There is limited information on the safety of tramadol use in pregnant women. Therefore, Tramadol Krka solution for injection/infusion should not be used in pregnant women. Long-term use of Tramadol Krka solution for injection/infusion during pregnancy may lead to dependence on tramadol in the unborn child, resulting in withdrawal symptoms in newborns. Tramadol is excreted into breast milk. Therefore, during breastfeeding, the patient should not take Tramadol Krka more than once, or if they have taken it more than once, they should stop breastfeeding. Observations in humans indicate that tramadol does not affect fertility in women and men.

Driving and using machines

Tramadol Krka solution for injection/infusion may cause drowsiness, dizziness, and blurred vision (impaired vision), and therefore may impair reactions. If such symptoms occur, the patient should not drive vehicles or operate machines.

Tramadol Krka contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per dose, which means it is essentially "sodium-free".

3. How to use Tramadol Krka

Tramadol Krka solution for injection/infusion should always be used as directed by the doctor. In case of doubts, the patient should consult their doctor, pharmacist, or nurse. Before starting treatment and regularly during treatment, the doctor will discuss with the patient what to expect from Tramadol Krka, when and for how long to take it, when to contact the doctor, and when to stop taking it (see also section 2). The dose should be adjusted based on the severity of pain and the patient's individual sensitivity to pain. The smallest dose that provides pain relief should be used. The patient should not take more than 8 mL of Tramadol Krka solution for injection/infusion per day (which corresponds to 400 mg of tramadol hydrochloride), unless the doctor recommends otherwise. Unless the doctor recommends otherwise, the recommended dose is: Adults and adolescents over 12 years of ageDepending on the severity of pain, usually 1-2 mL of Tramadol Krka solution for injection/infusion (corresponding to 50-100 mg of tramadol hydrochloride) is administered every 4-6 hours. The effect lasts for 4 to 6 hours. Detailed information on the use of Tramadol Krka solution for injection/infusion for doctors and qualified medical staff is provided at the end of this leaflet. ChildrenTramadol Krka solution for injection/infusion should not be used in children under 1 year of age. In children over 1 year of age and up to 11 years, the single dose is 1-2 mg of tramadol hydrochloride per kilogram of body weight. The smallest effective dose of the medicine should be used. The total daily dose should not exceed 8 mg of tramadol hydrochloride per kilogram of body weight or a total daily dose of 400 mg of tramadol hydrochloride. Detailed information on the use of Tramadol Krka solution for injection/infusion for doctors and qualified medical staff is provided at the end of this leaflet. Elderly patientsIn elderly patients (over 75 years), the elimination of tramadol may be delayed. In such cases, the doctor may recommend prolonging the interval between doses. Patient with severe liver or kidney impairment (failure) and (or) patients on dialysisTramadol Krka solution for injection/infusion should not be used in patients with severe liver or kidney failure. If the patient has mild or moderate impairment, the doctor may recommend prolonging the intervals between doses of the medicine. Administration How and when to take Tramadol Krka solution for injection/infusionTramadol Krka solution for injection/infusion is intended for intravenous, intramuscular, or subcutaneous administration (in the case of intravenous administration, Tramadol Krka solution for injection/infusion is usually injected into a superficial vein of the arm, during intramuscular administration mainly into the gluteal muscle, and subcutaneously - under the skin). Alternatively, Tramadol Krka solution for injection/infusion can be diluted and administered intravenously as a drip infusion. Detailed information on the use of Tramadol Krka solution for injection/infusion for doctors and qualified medical staff is provided at the end of this leaflet. How long to take Tramadol Krka solution for injection/infusionThe patient should not take Tramadol Krka solution for injection/infusion for longer than necessary. If long-term use is required, the doctor will regularly monitor the patient at short intervals (if necessary, after breaks in treatment) to determine whether continued use of tramadol in the form of a solution for injection/infusion is justified and what dose the patient should take. If the patient feels that the effect of Tramadol Krka solution for injection/infusion is too strong or too weak, they should consult their doctor, pharmacist, or nurse.

Taking a higher dose of Tramadol Krka than recommended

Accidental ingestion of an additional dose of Tramadol Krka solution for injection/infusion usually does not cause any side effects. The patient should take the next dose of Tramadol Krka solution for injection/infusion as recommended. If a dose significantly higher than recommended is taken, the following symptoms may occur: pupil constriction, vomiting, low blood pressure, rapid heartbeat, circulatory collapse, impaired consciousness leading to coma (deep loss of consciousness), seizures, and breathing difficulties leading to respiratory arrest. If these symptoms occur, the patient should immediately contact their doctor.

Missing a dose of Tramadol Krka

Stopping Tramadol Krka solution for injection/infusion may cause the pain to return. The patient should not take a double dose of the medicine to make up for the missed dose, but should continue taking the medicine as recommended.

Stopping Tramadol Krka

Stopping Tramadol Krka solution for injection/infusion too early or abruptly may cause the pain to return. The patient should not stop taking this medicine without their doctor's recommendation, especially if they have been taking it for a long time. The doctor will advise when and how to stop taking the medicine; this may involve gradually reducing the dose to minimize the risk of side effects (withdrawal symptoms). In general, after stopping Tramadol Krka solution for injection/infusion, no serious side effects are observed. However, in rare cases, after abrupt discontinuation of Tramadol Krka solution for injection/infusion used for a certain period, the patient may feel unwell. They may experience agitation, anxiety, nervousness, or tremors. Insomnia, restlessness, and gastrointestinal disorders are also possible. In rare cases, panic attacks, hallucinations, abnormal perception of stimuli (such as itching, tingling, and numbness), and "ringing" in the ears (tinnitus) may occur. Other unusual central nervous system disorders, such as confusion, delusions, changes in self-perception (depersonalization), and changes in the perception of reality (derealization), as well as persecutory delusions (paranoia), have occurred very rarely. If the patient experiences any of these symptoms after stopping Tramadol Krka solution for injection/infusion, they should consult their doctor. If the patient has any further doubts about using this medicine, they should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Tramadol Krka can cause side effects, although not everybody gets them.

The patient should immediately contact their doctor if they 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 of Tramadol Krka are nausea and dizziness, which occur in more than 1 in 10 patients.

Very common: may affect more than 1 in 10 patients

Dizziness, nausea.

Common: may affect up to 1 in 10 patients

Headache, drowsiness, fatigue, vomiting, constipation, dry mouth; excessive sweating.

Uncommon: may affect up to 1 in 100 patients

Affecting the cardiovascular system (palpitations, rapid heartbeat [tachycardia], dizziness [orthostatic hypotension] or circulatory collapse). These side effects may occur especially when standing and in patients after physical exertion. Vomiting reflex, gastrointestinal disorders (e.g., pressure in the stomach, bloating), diarrhea. Skin reactions (e.g., itching, rash).

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

Allergic reactions (e.g., difficulty breathing [dyspnea], wheezing, fluid retention [angioedema]) and shock (sudden circulatory failure) occur very rarely. Slowed heart rate (bradycardia). Increased blood pressure. Abnormal sensations on the skin (such as tingling, prickling, numbness), shivering (shaking), seizures, involuntary muscle contractions, impaired coordination, transient loss of consciousness (fainting), speech disorders. Seizures have occurred mainly after high doses of tramadol or after concomitant use of medicines that may cause seizures. Changes in appetite. Hallucinations, confusion, sleep disorders, delirium, anxiety, and nightmares. Psychiatric disorders may occur after treatment with Tramadol Krka solution for injection/infusion; their intensity and nature may vary depending on the patient's personality and the duration of treatment (depending on the patient's personality and treatment duration). They include changes in mood (usually excitement, sometimes dysphoria), changes in activity (usually decreased, sometimes increased), and changes in cognitive and sensory abilities (e.g., difficulties in making decisions, impaired perception). The medicine may cause dependence. After stopping treatment, withdrawal symptoms may occur (see "Stopping Tramadol Krka solution for injection/infusion"). Blurred vision, pupil constriction, pupil dilation. Slowed breathing (respiratory depression), breathing difficulties (dyspnea). In case of exceeding the recommended doses or concomitant use of other medicines with a depressant effect on brain function, respiratory depression may occur. There have been reports of worsening asthma, but no causal relationship with the active substance tramadol has been established. Muscle weakness. Difficulty or pain when urinating, decreased urine output (urination disorders and difficulty urinating).

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

Increased activity of liver enzymes.

Frequency not known: cannot be estimated from the available data

Low blood sugar. Hiccup. Serotonin syndrome, the symptoms of which may include changes in mental state (e.g., excitement, hallucinations, coma), as well as other symptoms, such as fever, rapid heartbeat, unstable blood pressure, involuntary muscle contractions, muscle stiffness, lack of coordination, and (or) gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "Important information before using Tramadol Krka").

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw Tel.: +48 22 49 21 301 Fax: +48 22 49 21 309 Website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Tramadol Krka

The medicine should be stored out of sight and reach of children. This medicine should be stored in a closed and secure place, inaccessible to other people. It can cause serious harm and be fatal to individuals for whom it has not been prescribed. The patient should not use this medicine after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of the month stated. There are no special storage precautions. Solutions for infusion showing chemical and physical stability for 24 hours at a temperature up to 25°C:

• 4.2% sodium bicarbonate solution
• Ringer's solution

Solutions for infusion showing chemical and physical stability for 5 days at a temperature up to 25°C:

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

From a microbiological point of view, the product should be used immediately. If the product is not used immediately, the responsibility for the storage time and conditions before use lies with the patient. The patient should not use this medicine if they notice that the solution is not clear and free from particles or if the container is damaged. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer use. This will help protect the environment.

6. Contents of the packaging and other information

What Tramadol Krka contains

• The active substance of Tramadol Krka is tramadol hydrochloride. Tramadol Krka 50 mg/mL solution for injection/infusion 1 mL of solution for injection/infusion (1 ampoule) contains 50 mg of tramadol hydrochloride. Tramadol Krka 100 mg/2 mL solution for injection/infusion 2 mL of solution for injection/infusion (1 ampoule) contains 100 mg of tramadol hydrochloride. 1 mL of solution for injection/infusion contains 50 mg of tramadol hydrochloride.
• The other ingredients are anhydrous sodium acetate and water for injection. See section 2 "Tramadol Krka contains sodium".

What Tramadol Krka looks like and contents of the pack

The solution for injection/infusion is a clear, colorless solution, practically free from particles. Tramadol Krka 50 mg/mL solution for injection/infusion 1, 5, 10, 20, 25, and 100 ampoules in a cardboard box (packaged in PVC/Aluminum blisters), each containing 1 mL of solution for injection/infusion. The ampoules are marked with a red dot and a blue ring. Tramadol Krka 100 mg/2 mL solution for injection/infusion 1, 5, 10, 20, 25, and 100 ampoules in a cardboard box (packaged in PVC/Aluminum blisters), each containing 2 mL of solution for injection/infusion. The ampoules are marked with a red dot and a green ring. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

KRKA, d.d., Novo mesto Šmarješka cesta 6 8501 Novo mesto Slovenia For more detailed information on the names of the medicine in other EU member states, the patient should contact the local representative of the marketing authorization holder: KRKA-POLSKA Sp. z o.o. ul. Równoległa 5 02-235 Warsaw Tel. 22 57 37 500

Date of last revision of the leaflet: 19.07.2024

-------------------------------------------------------------------------------------------------------------------------- Information intended for healthcare professionals only:

Tramadol Krka 50 mg/mL solution for injection/infusion

Tramadol Krka 100 mg/2 mL solution for injection/infusion

Tramadol hydrochloride

Information on opening the ampoule

The ampoule has a marked break point, which allows for easy opening without the use of tools.

• 1. The ampoule should be turned until the marked break point is facing upwards.
• 2. The top of the ampoule should be broken off.

Further information on administration

In case of moderate pain, 1 mL of Tramadol Krka solution for injection/infusion (corresponding to 50 mg of tramadol hydrochloride) is administered. If the pain does not subside after 30-60 minutes, 1 mL can be administered again. In case of severe pain, the need for the medicine may be higher. Then, 2 mL of Tramadol Krka solution for injection/infusion (corresponding to 100 mg of tramadol hydrochloride) is administered as a single dose. Treatment of severe postoperative pain: it may be necessary to administer higher doses in an "on-demand" scheme (pain treatment according to needs) in the early postoperative period. The requirements during the 24-hour period are usually not higher than in the case of conventional administration. Tramadol Krka solution for injection/infusion is intended for intravenous, intramuscular, or subcutaneous administration (in the case of intravenous administration, Tramadol Krka solution for injection/infusion is usually injected into a superficial vein of the arm, during intramuscular administration mainly into the gluteal muscle, and subcutaneously - under the skin). Alternatively, Tramadol Krka solution for injection/infusion can be diluted and administered intravenously as a drip infusion. Intravenous administration of the medicine should be slow, i.e., 1 mL of Tramadol Krka solution for injection/infusion (corresponding to 50 mg of tramadol hydrochloride) per minute. Tramadol Krka solution for injection/infusion can be diluted with an appropriate solution for injection (e.g., 4.2% sodium bicarbonate solution, Ringer's solution, 0.9% sodium chloride solution, 0.18% sodium chloride and 4% glucose solution, sodium lactate solution, 5% glucose solution) and administered as an intravenous drip infusion or patient-controlled analgesia (PCA).

Incompatibility of Tramadol Krka solution for injection/infusion

This medicine should not be mixed with other medicines, except for those listed in this section ("Further information on administration").

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

Calculations for the volume of the solution for injection

• 1) calculation of the required total dose of tramadol hydrochloride (mg): body weight (kg) x dose (mg/kg body weight).
• 2) calculation of the volume of the diluted solution for injection/infusion of tramadol hydrochloride to be administered: divide the total dose (mg) by the appropriate concentration of the diluted solution (mg/mL, see the table below).

In this case, Tramadol Krka solution for injection/infusion is diluted with water for injection. The following scheme shows the concentrations achieved: Dilution of Tramadol Krka 50 mg/mL solution for injection/infusion and Tramadol Krka 100 mg/2 mL solution for injection/infusion:

Example: Administration of a dose of 1.5 mg of tramadol hydrochloride per kilogram of body weight in a child weighing 45 kg. It is necessary to administer 67.5 mg of tramadol hydrochloride. For this purpose, 2 mL of Tramadol Krka 50 mg/mL solution for injection/infusion (corresponding to 2 ampoules of 1 mL) or 2 mL of Tramadol Krka 100 mg/2 mL solution for injection/infusion (corresponding to 1 ampoule of 2 mL) should be diluted with 4 mL of water for injection. This gives a concentration of 16.7 mg/mL of tramadol hydrochloride. The patient should administer 4 mL of the diluted solution (approximately 67 mg of tramadol hydrochloride).