Tramadol krka

Package leaflet: Information for the patient

Tramadol Krka 50 mg/mL solution for injection/infusion
Tramadol Krka 100 mg/2 mL solution for injection/infusion
tramadoli hydrochloridum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Tramadol Krka is and what it is used for
2. What you need to know before you use Tramadol Krka
3. How to use Tramadol Krka
4. Possible side effects
5. How to store Tramadol Krka
6. Contents of the pack and other information

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

Tramadol – the active substance in Tramadol Krka solution for injection/infusion – is an analgesic medicine belonging to the opioid class acting on the central nervous system. It relieves pain by acting on specific nerve cells in the spinal cord and brain.
Tramadol Krka solution for injection/infusion is used in the treatment of moderate to severe pain.

2. Important information before using Tramadol Krka

When not to use Tramadol Krka

• if the patient is allergic to tramadol or to any of the other ingredients of this medicine (listed in section 6);
• in case of acute alcohol intoxication, hypnotics, analgesics or other psychotropic medicines (medicines affecting mood and emotions);
• if the patient is also taking MAO inhibitors (certain medicines used to treat depression) or has taken them within the last two weeks before starting treatment (see "Tramadol Krka and other medicines");
• if the patient has epilepsy and seizures are not adequately controlled by effective therapy;
• as substitution therapy in the treatment of opioid dependence.

Warnings and precautions
Before starting treatment with Tramadol Krka injection/infusion solution, inform your doctor or pharmacist:

• if the patient suspects dependence on other painkillers (opioids);
• if the patient experiences disturbances in consciousness (feeling similar to fainting);
• if the patient is in shock (one of the symptoms may be cold sweats);
• if the patient has increased intracranial pressure (which may be caused by head injury or brain diseases);
• if the patient has breathing difficulties;
• if the patient has a tendency to develop seizures or convulsions;
• if the patient has liver or kidney disease;
• if the patient has depression and is taking antidepressants, as some of them may interact with tramadol (see "Tramadol Krka and other medicines").

Serotonin syndrome
There is a small risk of so-called serotonin syndrome when tramadol is taken together with certain antidepressants or tramadol alone. If the patient experiences any symptoms of this serious condition, he or she should seek immediate medical advice (see section 4 "Possible side effects").

Sleep-related breathing disorders
Tramadol Krka may cause breathing disorders during sleep, such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood).
Symptoms may include pauses in breathing during sleep, nocturnal awakenings due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If the patient or someone else observes these symptoms, contact a doctor. The doctor may recommend reducing the dose.

Seizures have been reported in patients taking tramadol at the recommended dose. This risk may increase if the recommended maximum daily dose of tramadol (400 mg) is exceeded.

Tolerance, dependence and abuse
This medicine contains tramadol, which is an opioid medicine. Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient's body becomes accustomed to the medicine, known as tolerance). Repeated use of Tramadol Krka may also lead to dependence, misuse and abuse, which may result in life-threatening overdose. The risk of these adverse effects may increase with higher doses and longer duration of treatment.

Dependence or abuse may cause the patient to lose control over the amount or frequency of medicine intake.

The risk of dependence or abuse varies among individuals. Higher risk of dependence on Tramadol Krka may apply to individuals in the following situations:

• the patient or someone in their family has ever misused or been dependent on alcohol, prescription medicines or illegal drugs ("abuse");
• the patient is a tobacco smoker;
• the patient has ever had mood problems (depression, anxiety or personality disorders) or has been treated by a psychiatrist for other mental illnesses.

If the patient notices any of the following symptoms while taking Tramadol Krka, this may indicate dependence or abuse:

• 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, e.g. "to calm down" or "to sleep better".
• The patient has made repeated, unsuccessful attempts to stop or control use of the medicine.
• After stopping the medicine, the patient feels unwell, and feels better after taking the medicine again ("withdrawal effects").

If the patient notices any of these symptoms, he or she should consult a doctor to discuss the best treatment approach, including when and how to stop taking the medicine safely (see section 3, "Stopping treatment with Tramadol Krka").

If any of these problems occur during treatment with Tramadol Krka injection/infusion solution or have occurred in the past, inform the doctor, pharmacist or nurse.

Contact a doctor if, during treatment with Tramadol Krka, the patient experiences any of the following symptoms:
Excessive fatigue, loss of appetite, severe abdominal pain, nausea, vomiting or low blood pressure.
This may indicate adrenal insufficiency (low cortisol levels). If such symptoms occur, contact a doctor, who will decide whether hormone replacement is necessary.

Tramadol is metabolized in the liver by an enzyme. Some people have a genetic variation of this enzyme, which may lead to different effects. In some individuals, pain relief may be insufficient, while in others, severe adverse effects may be more likely.

Stop using the medicine and contact a doctor immediately if the patient experiences any of the following adverse effects: slowed or shallow breathing, confusion, drowsiness, pinpoint pupils, nausea or vomiting, constipation, loss of appetite.

Children and adolescents
This medicine should not be given to children under 1 year of age.

Use in children with breathing disorders
Tramadol is not recommended in children with breathing disorders, as symptoms of tramadol toxicity may be more pronounced in them.

Tramadol Krka and other medicines
Inform your doctor, pharmacist or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

Tramadol Krka injection/infusion solution should not be used simultaneously with MAO inhibitors (certain medicines used to treat depression) (see "When not to use Tramadol Krka").

The analgesic effect of Tramadol Krka injection/infusion solution may be reduced and/or its duration shortened when taken simultaneously with medicines containing:

• carbamazepine (used in the treatment of epileptic seizures),
• ondansetron (an antiemetic).

The doctor will determine whether the patient can use Tramadol Krka injection/infusion solution and at what dose.

Concomitant use of Tramadol Krka and sedative medicines such as benzodiazepines or similar medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma and may be life-threatening. Therefore, concomitant use of these medicines should only be considered when other treatment options are not possible.

If the doctor prescribes Tramadol Krka together with sedative medicines, the dose and duration of concomitant use should be minimized.

Inform the doctor about all sedative medicines the patient is taking and strictly follow dosing instructions. It may be helpful to inform friends or family members so they are aware of these symptoms. If such symptoms occur, contact a doctor.

The risk of adverse effects increases:

• when Tramadol Krka injection/infusion solution is used concomitantly with medicines that depress brain function. Dizziness and fainting may occur. In such cases, consult a doctor. Other medicines include sleeping pills and certain analgesics such as morphine and codeine (which also have antitussive effects), as well as alcohol.
• if the patient takes other medicines that may cause seizures (fits), such as certain antidepressants or antipsychotics. The risk of seizures may increase if the patient takes Tramadol Krka injection/infusion solution simultaneously with these medicines. The doctor should inform the patient whether Tramadol Krka injection/infusion solution is suitable for them.
• if the patient takes certain antidepressants. Tramadol Krka may interact with these medicines and cause serotonin syndrome (see section 4 "Possible side effects").
• if the patient takes anticoagulants which are coumarin derivatives, such as warfarin (medicines that reduce blood clotting), concomitantly with Tramadol Krka injection/infusion solution. The anticoagulant effect of these medicines may be disturbed, leading to bleeding.
• if the patient takes gabapentin or pregabalin for the treatment of epilepsy or nerve-related pain (neuropathic pain).

Tramadol Krka with food, drink and alcohol
Do not drink alcohol during treatment with Tramadol Krka injection/infusion solution, as it may enhance its effects. Food does not affect the action of Tramadol Krka injection/infusion solution.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult a doctor, pharmacist or nurse before using this medicine.

There is limited information on the safety of tramadol use in pregnant women. Therefore, Tramadol Krka injection/infusion solution should not be used in pregnant patients.

Long-term use of Tramadol Krka injection/infusion solution during pregnancy may lead to tramadol dependence in the unborn child and, consequently, withdrawal symptoms in newborns.

Tramadol is excreted in breast milk. Therefore, during breastfeeding, Tramadol Krka should not be taken more than once, or if Tramadol Krka has been taken more than once, breastfeeding should be discontinued.

Observations on the use of tramadol in humans indicate that tramadol does not affect fertility in women and men.

Driving and using machines
Tramadol Krka injection/infusion solution may cause drowsiness, dizziness and visual disturbances (blurred vision), thus impairing reaction ability. If such symptoms occur, do not drive or operate machinery.

Tramadol Krka contains sodium
The medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e. the medicine is considered "sodium-free".

3. How to use Tramadol Krka

Tramadol Krka solution for injection/infusion must always be used exactly as directed by the physician. If in doubt, consult your doctor, pharmacist, or nurse.
Before starting treatment and regularly during treatment, the doctor will discuss with the patient what to expect from using Tramadol Krka, when and for how long the medicine should be taken, when to contact the doctor, and when the medicine should be discontinued (see also section 2).
Dosage should be adjusted according to the intensity of pain and the individual patient's sensitivity to pain. The lowest effective dose providing adequate pain relief should usually be used. Do not take more than 8 ml of Tramadol Krka solution for injection/infusion per day (corresponding to 400 mg of tramadol hydrochloride), unless otherwise directed by the physician.
Unless otherwise prescribed by the physician, the usual recommended dose is:
Adults and adolescents over 12 years of age
Depending on the severity of pain, 1–2 ml of Tramadol Krka solution for injection/infusion (equivalent to 50–100 mg of tramadol hydrochloride) is usually administered every 4 to 6 hours.
The duration of action varies depending on the pain and typically lasts from 4 to 6 hours.
Detailed information on the administration of Tramadol Krka solution for injection/infusion for physicians and qualified medical personnel is provided at the end of this leaflet.
Children
Tramadol Krka solution for injection/infusion must not be used in children under 1 year of age.
In children aged over 1 year up to 11 years, the single dose is 1 to 2 mg of tramadol hydrochloride per kilogram of body weight. The lowest effective dose should be used.
The total daily dose must 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 administration of Tramadol Krka solution for injection/infusion for physicians and qualified medical personnel is provided at the end of this leaflet.
Elderly patients
In elderly patients (over 75 years of age), elimination of tramadol may be delayed. In such cases, the physician may recommend extending the interval between doses.
Patients with severe hepatic or renal impairment (failure) and (or) dialysis patients
Tramadol Krka must not be used in patients with severe hepatic and (or) renal failure.
If the patient has mild or moderate impairment, the physician may recommend prolonging the intervals between doses.
Method of administration
How and when to administer Tramadol Krka solution for injection/infusion
Tramadol Krka solution for injection/infusion is intended for intravenous, intramuscular, or subcutaneous administration (in intravenous administration, Tramadol Krka solution for injection/infusion is usually injected into a superficial vein of the arm; for intramuscular administration, mainly into the gluteal muscle; and for subcutaneous administration, under the skin).
Alternatively, Tramadol Krka solution for injection/infusion may be diluted and administered intravenously as an infusion. Detailed information on the administration of Tramadol Krka solution for injection/infusion for physicians and qualified medical personnel is provided at the end of this leaflet.
How long to use Tramadol Krka solution for injection/infusion
Do not use Tramadol Krka solution for injection/infusion for longer than necessary. If long-term treatment is required, the physician will regularly monitor, at short intervals (and if necessary, after treatment breaks), whether continued use of tramadol solution for injection/infusion is indicated and what dose the patient should receive.
If the patient feels that the effect of Tramadol Krka solution for injection/infusion is too strong or too weak, consult the doctor, pharmacist, or nurse.
Use of a higher than recommended dose of Tramadol Krka
Accidental intake of an additional dose of Tramadol Krka solution for injection/infusion usually does not cause any adverse effects. The next dose of Tramadol Krka solution for injection/infusion should be taken according to the prescribed schedule.
If a dose significantly higher than recommended is taken, symptoms such as pinpoint pupils, vomiting, hypotension, tachycardia, circulatory collapse, disturbances of consciousness leading to coma (deep loss of consciousness), seizures, and breathing difficulties leading to respiratory arrest may occur. If these symptoms occur, contact a doctor immediately.
Missing a dose of Tramadol Krka
Interrupting the use of Tramadol Krka solution for injection/infusion may cause recurrence of pain. Do not take a double dose to make up for a missed dose; continue taking the medicine as prescribed.
Stopping treatment with Tramadol Krka
Premature discontinuation or termination of treatment with Tramadol Krka solution for injection/infusion will likely result in recurrence of pain.
Do not abruptly stop using this medicine without medical advice. If the patient wishes to discontinue the medicine, especially after long-term use, this should be discussed with the doctor. The doctor will advise when and how to stop the medicine, which may involve gradually reducing the dose to minimize the risk of adverse effects (withdrawal symptoms).
Generally, no serious post-treatment symptoms are observed after discontinuation of Tramadol Krka solution for injection/infusion. However, in rare cases, after abrupt discontinuation of Tramadol Krka solution for injection/infusion following prolonged use, the patient may feel unwell. Symptoms may include restlessness, anxiety, nervousness, or tremor. Hyperactivity, difficulty sleeping, and gastrointestinal disturbances may also occur. Rarely, panic attacks, hallucinations, abnormal sensory perceptions such as itching, tingling, and numbness, as well as tinnitus (ringing in the ears) may occur. Other very rare central nervous system disturbances include confusion, delusions, altered perception of self (depersonalization), altered perception of reality (derealization), and persecutory delusions (paranoia). If any of these symptoms occur after discontinuation of Tramadol Krka solution for injection/infusion, consult a 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 may cause adverse effects, although not everyone will experience them.
You should contact your doctor immediately if symptoms of an allergic reaction occur, such as
facial swelling, swelling of the tongue and (or) throat), and (or) difficulty swallowing or hives
with breathing difficulties.
The most common adverse effects during treatment with Tramadol Krka are nausea
and dizziness, occurring 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
Effects on cardiovascular regulation (palpitations, increased heart rate [tachycardia], dizziness [orthostatic hypotension] or circulatory collapse). These adverse effects may occur especially in the standing position and in patients after physical exertion.
Vomiting reflex, gastrointestinal disturbances (e.g. stomach discomfort, bloating), diarrhoea.
Skin reactions (e.g. itching, rash).
Rare: may affect up to 1 in 1,000 patients
Allergic reactions (e.g. breathing difficulties [dyspnoea], wheezing, fluid retention in tissues [angioedema]) and shock (sudden circulatory failure) occur very rarely.
Slowing of heart rate (bradycardia).
Increased blood pressure.
Abnormal skin sensations (such as tingling, pricking, numbness), chills (tremor), seizures, involuntary muscle contractions, impaired coordination, transient loss of consciousness (fainting), speech disorders.
Seizures occurred mainly after administration of high doses of tramadol or when used concomitantly with medicines that may provoke seizures.
Changes in appetite.
Hallucinations, confusion, sleep disturbances, delirium, restlessness and nightmares.
Psychiatric disorders may occur after treatment with Tramadol Krka injection/infusion solution; their intensity and character may vary among individual patients (depending on the patient's personality and duration of treatment). These include mood changes (usually excitement, sometimes dysphoria), changes in activity (usually reduced, occasionally increased) and changes in cognitive functions and sensory performance (e.g. difficulty making decisions, perception disturbances).
The medicine may cause dependence.
Reactions related to discontinuation of the medicine may occur after stopping treatment (see "Stopping treatment with Tramadol Krka injection/infusion solution").
Blurred vision, constricted pupils, dilated pupils.
Slowed breathing (respiratory depression), difficulty breathing (dyspnoea).
Respiratory depression may occur when recommended doses are exceeded or when other medicines with central nervous system depressant effects are administered concomitantly.
Cases of asthma exacerbation have been reported, but a causal relationship with the active substance tramadol has not been established.
Reduced muscle strength.
Difficulty or pain during urination, reduced urine volume (urinary disorders and difficulty passing urine).
Very rare: may affect up to 1 in 10,000 patients
Increased liver enzyme activity.
Frequency not known: cannot be determined from available data
Low blood sugar levels.
Hiccups.
Serotonin syndrome, which may present with changes in mental status (e.g. agitation, hallucinations, coma), as well as other symptoms such as fever, rapid heartbeat, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination and (or) gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2 "Important information before using Tramadol Krka").
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Tramadol Krka

Keep this medicine out of sight and reach of children.
This medicine should be stored in a closed and secure place inaccessible to others. It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the packaging following the abbreviation EXP. The expiry date refers to the last day of the specified month.
No special storage instructions apply.
Infusion solutions demonstrating chemical and physical stability for 24 hours at temperatures up to 25°C:

• 4.2% sodium bicarbonate solution
• Ringer's solution

Infusion solutions demonstrating chemical and physical stability for 5 days at temperatures up to 25°C:

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

From a microbiological standpoint, the product should be used immediately. If the product is not used immediately, the responsibility for storage conditions and duration prior to use lies with the user.
Do not use this medicine if 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. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Tramadol Krka contains

• The active substance is tramadol hydrochloride. Tramadol Krka 50 mg/mL solution for injection/infusion contains 50 mg of tramadol hydrochloride per 1 ml of solution for injection/infusion (1 ampoule). Tramadol Krka 100 mg/2 mL solution for injection/infusion contains 100 mg of tramadol hydrochloride per 2 ml of solution for injection/infusion (1 ampoule). 1 ml of solution for injection/infusion contains 50 mg of tramadol hydrochloride.
• The other ingredients are anhydrous sodium acetate and water for injections. 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, colourless 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 (packed in blisters made of PVC/Aluminium),
each containing 1 ml of solution for injection/infusion. 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 (packed in blisters made of PVC/Aluminium),
each containing 2 ml of solution for injection/infusion. Ampoules are marked with a red dot and a green ring.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto
Slovenia
For more detailed information on the product names in other European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5 Street
02-235 Warsaw
Tel. 22 57 37 500

Information intended exclusively for medical professionals:

Tramadol Krka 50 mg/mL solution for injection/infusion
Tramadol Krka 100 mg/2 mL solution for injection/infusion
tramadoli hydrochloridum

Information on how to open the ampoule
The ampoule has a marked break point, which allows easy opening without the use of tools.

1. Rotate the ampoule until the marked point is facing upwards.
2. Break off the top of the ampoule.

Further information on administration
For moderate pain, administer 1 mL of Tramadol Krka solution for injection/infusion (corresponding to 50 mg of tramadol hydrochloride). If pain has not subsided after 30–60 minutes, the dose may be repeated.
For severe pain, a higher dose may be required. In such cases, administer 2 mL of Tramadol Krka solution for injection/infusion (corresponding to 100 mg of tramadol hydrochloride) as a single dose.
Treatment of severe postoperative pain: higher doses may be necessary using an "on-demand" regimen (pain treatment according to individual needs), particularly in the early postoperative period. However, 24-hour requirements are generally not higher than with conventional administration.
Tramadol Krka solution for injection/infusion is intended for intravenous, intramuscular, or subcutaneous administration (for intravenous administration, Tramadol Krka solution for injection/infusion is usually injected into a superficial vein of the arm; for intramuscular administration, primarily into the gluteal muscle; and for subcutaneous administration, under the skin).
Intravenous administration of the solution should be slow, i.e., 1 mL of Tramadol Krka solution for injection/infusion (corresponding to 50 mg of tramadol hydrochloride) per minute.
Alternatively, Tramadol Krka solution for injection/infusion may be diluted with an appropriate injection solution (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 infusion or via patient-controlled analgesia (PCA).

Pharmaceutical incompatibilities of Tramadol Krka solution for injection/infusion
This medicinal product must not be mixed with other medicinal products except those mentioned in this section ("Further information on administration").

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

Calculations for injection solution volume

1. Calculate the required total dose of tramadol hydrochloride (mg): body weight (kg) × dose (mg/kg body weight).
2. Calculate the volume of diluted tramadol hydrochloride injection/infusion solution to be administered:
   Divide the total dose (mg) by the appropriate concentration of the diluted solution (mg/mL; see table below).
   To achieve this, Tramadol Krka solution for injection/infusion is diluted with water for injections.
   The following table shows the resulting concentrations (1 mL of Tramadol Krka solution for injection/infusion contains 50 mg of tramadol hydrochloride):

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. To achieve this, dilute 2 ml of the medicinal product Tramadol Krka 50 mg/mL solution for injection/infusion (corresponding to 2 ampoules of 1 ml) or 2 ml of the medicinal product Tramadol Krka 100 mg/2 mL solution for injection/infusion (corresponding to 1 ampoule of 2 ml) with 4 ml of water for injections. This yields a concentration of 16.7 mg/ml of tramadol hydrochloride. Administer 4 ml of the diluted solution (approximately 67 mg of tramadol hydrochloride).