TRAMADOL/DEXKETOPROFEN KRKA 75 mg/25 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Tramadol/Dexketoprofen Krka 75 mg/25 mg Film-Coated Tablets EFG

tramadol hydrochloride/dexketoprofen

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Tramadol/Dexketoprofen Krka contains the active substances tramadol hydrochloride and dexketoprofen. Tramadol hydrochloride is a pain reliever belonging to the group of opioids that act on the central nervous system. It relieves pain by acting on specific nerve cells in the brain and spinal cord.

Dexketoprofen is a pain reliever belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs).

Tramadol/dexketoprofen is used for the symptomatic treatment of short-term moderate to severe acute pain in adults.

You should consult a doctor if you do not feel better or if you get worse.

2. What you need to know before you take Tramadol/Dexketoprofen Krka

Do not takeTramadol/Dexketoprofen Krka

• if you are allergic to tramadol hydrochloride, dexketoprofen or any of the other ingredients of this medicine (listed in section 6),
• if you are allergic to acetylsalicylic acid or other NSAIDs,
• if you have had asthma attacks, acute allergic rhinitis (a short period of inflammation of the nasal mucosa), nasal polyps (fleshy growths inside the nose due to allergy), urticaria (rash), angioedema (swelling of the face, eyes, lips or tongue, or difficulty breathing) or wheezing in the chest after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs,
• if you have had photoallergic or phototoxic reactions (redness and/or blistering of the skin exposed to sunlight) while taking ketoprofen (an NSAID) or fibrates (medicines used to reduce blood fat levels),
• if you have a peptic ulcer, stomach or intestinal bleeding or if you have had bleeding, ulceration or perforation of the stomach or intestine in the past, including if it is due to previous use of NSAIDs,
• if you have chronic digestive problems (e.g. indigestion, heartburn),
• if you have chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis),
• if you have severe heart failure, moderate to severe renal impairment or severe hepatic impairment,
• if you have bleeding disorders or blood coagulation disorders,
• if you are severely dehydrated (have lost a lot of body fluid) due to vomiting, diarrhea or insufficient fluid intake,
• if you have acute alcohol intoxication, sleeping pills, painkillers, or medications that affect mood and emotions,
• if you are also taking monoamine oxidase inhibitors (MAOIs) (certain medications used to treat depression) or if you have taken them in the last 14 days before starting treatment with this medicine (see "Other medicines and Tramadol/Dexketoprofen Krka"),
• if you have epilepsy or suffer from convulsive seizures, because the risk of these seizures may increase,
• if you have difficulty breathing,
• if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor before starting to take this medicine:

• if you are allergic or have had allergy problems in the past,
• if you have kidney, liver or heart disease (hypertension and/or heart failure), as well as fluid retention or have had any of these diseases in the past,
• if you are taking diuretics,
• if you have heart problems, a history of strokes, or think you may be at risk of suffering from these disorders (e.g. if you have high blood pressure, diabetes, high cholesterol or are a smoker) you should consult this treatment with your doctor. Medicines like this one can be associated with a small increase in the risk of suffering heart attacks (myocardial infarctions) or stroke. Any risk is more likely to occur when high doses are used and treatments are prolonged. Do not exceed the recommended dose or treatment duration,
• if you are an elderly patient: you may suffer from a higher incidence of side effects (see section 4). If these occur, consult your doctor immediately,
• if you are a woman with fertility problems: this medicine may affect your fertility, so you should not take it if you are planning to become pregnant or if you are undergoing fertility studies,
• if you have a blood disorder and blood cell disorder,
• if you have systemic lupus erythematosus or mixed connective tissue disease (diseases of the immune system that affect connective tissue),
• if you have had chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the past,
• if you suffer from or have had stomach or intestinal disorders in the past,
• if you have an infection; see the "Infections" heading below,
• if you are taking other medicines that increase the risk of peptic ulcer or bleeding, for example, oral corticosteroids, some antidepressants (of the SSRI type, Selective Serotonin Reuptake Inhibitors), agents that prevent clot formation such as acetylsalicylic acid or anticoagulants like warfarin. In these cases, consult your doctor before taking this medicine: it may be that your doctor prescribes an additional medicine to protect your stomach,
• if you suffer from depression and are taking antidepressants, as some may interact with tramadol (see "Other medicines and Tramadol/Dexketoprofen Krka"),
• if you are taking other medicines that contain the same active substances as this medicine, do not exceed the maximum daily dose of dexketoprofen or tramadol,
• if you think you are addicted to other painkillers (opioids),
• if you have altered consciousness (if you feel like you are going to faint),
• if you are in a state of shock (a sign of this state may be cold sweat),
• if you have increased intracranial pressure (possibly after a head injury or brain disease),
• if you have difficulty breathing,
• if you suffer from porphyria.

Tramadol can cause physical and psychological dependence. When this medicine is taken for a prolonged period, its effect may decrease, and higher doses may be necessary (development of tolerance). In patients with a tendency to abuse medicines or those with drug dependence, treatment with tramadol/dexketoprofen should only be carried out for short periods and under strict medical control. Inform your doctor if any of these problems appear during treatment with tramadol/dexketoprofen or if they appeared in the past.

Talk to your doctor if you experience any of the following symptoms while taking tramadol/dexketoprofen: 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 present any of these symptoms, inform your doctor, he will decide if you should take a hormonal supplement.

Tramadol is transformed in the liver by an enzyme. Some people have a variation of this enzyme, and this can affect each person differently. In some people, sufficient pain relief may not be achieved, while others are more likely to suffer from serious side effects. If you notice any of the following side effects, you should 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.

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 alone. Consult your doctor immediately if you present any of the symptoms related to this serious syndrome (see section 4 "Possible side effects").

Respiratory disorders related to sleep

Tramadol/dexketoprofen may cause sleep-related respiratory disorders such as central sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). These symptoms can be pauses in breathing during sleep, nocturnal awakening due to difficulty breathing, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, consult your doctor. Your doctor may consider reducing the dose.

Infections

Tramadol/dexketoprofen may mask the signs of an infection, such as fever or pain. Consequently, tramadol/dexketoprofen may delay the appropriate treatment of the infection, which can increase the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to chickenpox. If you take this medicine while you have an infection and the symptoms of the infection persist or worsen, consult a doctor without delay.

During chickenpox, it is recommended to avoid using this medicine.

Children and adolescents

This medicine has not been studied in children or adolescents. Therefore, safety and efficacy have not been established, and the medicine should not be used in children or adolescents.

Use in children with respiratory problems

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

Other medicines and Tramadol/Dexketoprofen Krka

Tell your doctor if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. There are some medicines that should not be taken together, and others that may require a dose adjustment if taken together.

Always inform your doctor if, in addition to tramadol/dexketoprofen, you are taking any of the following medicines:

The use oftramadol/dexketoprofenis not recommended with:

• Acetylsalicylic acid, corticosteroids, or other anti-inflammatory medicines,
• Warfarin, heparin, or other medicines used to prevent clot formation,
• Lithium, used to treat certain mood disorders,
• Methotrexate, used for rheumatoid arthritis and cancer,
• Hydantoins and phenytoin, used for epilepsy,
• Sulfamethoxazole, used for bacterial infections,
• Monoamine oxidase inhibitors (MAOIs) (medicines for the treatment of depression).

The use oftramadol/dexketoprofenrequires caution with:

• ACE inhibitors, diuretics, beta-blockers, and angiotensin II antagonists, used for high blood pressure and heart disorders,
• Pentoxifylline, used to treat chronic venous ulcers,
• Zidovudine, used to treat viral infections,
• Chlorpropamide and glibenclamide, used for diabetes,
• Aminoglycoside antibiotics, used for bacterial infections,
• The concomitant use of tramadol/dexketoprofen and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and can be potentially fatal. Due to this, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes tramadol/dexketoprofen along with sedative medicines, the dose and duration of concomitant treatment should be limited. Inform your doctor about all sedative medicines you are taking and carefully follow the recommended dose by your doctor. It may be helpful to inform friends or family members to be aware of the signs and symptoms indicated above. Contact your doctor when you experience these symptoms.

The use oftramadol/dexketoprofenshould be taken into account with:

• Quinolones (e.g. ciprofloxacin, levofloxacin) used for bacterial infections,
• Cyclosporine or tacrolimus, used to treat immune system diseases and organ transplants,
• Streptokinase and other thrombolytic and fibrinolytic medicines; i.e. medicines used to dissolve clots,
• Probenecid, used for gout,
• Digoxin, used in the treatment of chronic heart failure,
• Mifepristone, used for abortion,
• Antidepressants of the SSRI type (Selective Serotonin Reuptake Inhibitors),
• Antiplatelet agents used to reduce platelet aggregation and clot formation,
• Tenofovir, deferasirox, pemetrexed.

The analgesic effect of tramadol may be reduced, and the duration of action decreased if you also take medicines that contain:

• Carbamazepine (for epileptic seizures),
• Buprenorphine, nalbuphine, or pentazocine (pain relievers),
• Ondansetron (prevents nausea).

The risk of side effects increases:

• if you take tranquilizers, sleeping pills, other painkillers such as morphine and codeine (also as a cough medicine), or alcohol while taking tramadol/dexketoprofen. You may feel drowsy or feel like you could faint. Consult your doctor if this occurs.
• if you are taking medicines that can cause seizures (attacks), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take tramadol/dexketoprofen at the same time. Your doctor will inform you if tramadol/dexketoprofen is suitable for you.
• if you are taking certain antidepressants. Tramadol/dexketoprofen may interact with these medicines, and you may experience a serotonin syndrome (see section 4 "Possible side effects").
• if you take anticoagulants (medicines to thin the blood), e.g. warfarin, along with this medicine. The effect of these medicines may affect blood coagulation and may cause bleeding.

Taking Tramadol/Dexketoprofen Krka with alcohol

Do not drink alcohol during treatment with tramadol/dexketoprofen, as it may increase the effect of the medicine.

For instructions on how to take Tramadol/Dexketoprofen Krka, see section 3.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Dexketoprofen may cause kidney and heart problems in your fetus. It may affect your and your baby's tendency to bleed and delay or prolong labor more than expected. From the 20th week of pregnancy, dexketoprofen may cause kidney problems in your fetus, which can cause low levels of amniotic fluid surrounding the baby (oligohydramnios) or constriction of a blood vessel (ductus arteriosus) in the baby's heart.

Tramadol is excreted in breast milk.

The use of tramadol/dexketoprofen is contraindicated in pregnancy and during breastfeeding.

Driving and using machines

Tramadol/dexketoprofen may affect your ability to drive and use machines, as it can cause dizziness, blurred vision, or drowsiness as side effects of treatment. This happens mainly when tramadol/dexketoprofen is taken with medicines that affect mood and emotions or when taken with alcohol.

If you are affected, do not drive or use machines until the symptoms disappear.

Tramadol/Dexketoprofeno Krka contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; i.e. it is essentially "sodium-free".

Use in athletes

Athletes are warned that this medicine contains tramadol, a component that can result in a positive doping test.

3. How to take Tramadol/Dexketoprofen Krka

Follow the administration instructions for this medication exactly as indicated by your doctor. In case of doubt, consult your doctor again.

The effective lowest dose should be used for the shortest time necessary to relieve symptoms. If you have an infection, consult your doctor without delay if symptoms (such as fever and pain) persist or worsen (see section 2).

The dose of tramadol/dexketoprofen you need may vary, depending on the type, intensity, and duration of the pain. Your doctor will tell you how many tablets to take per day and for how long.

The recommended dose is generally 1 film-coated tablet (corresponding to 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen) every 8 hours, not exceeding 3 film-coated tablets per day (corresponding to 225 mg of tramadol hydrochloride and 75 mg of dexketoprofen) and not exceeding 5 days of treatment.

Use in children and adolescents

Tramadol/dexketoprofen is not suitable for children and adolescents.

Elderly patients

If you are 75 years or older, your doctor may recommend prolonging the dosing interval, as your body may eliminate the medication more slowly.

Patients with severe liver or kidney disease/dialysis:

Patients with severe liver and/or kidney insufficiency should not take tramadol/dexketoprofen.

In case of renal dysfunction, if in your case the insufficiency is mild, your doctor may recommend prolonging the dosing interval.

In case of liver dysfunction, if in your case the insufficiency is mild or moderate, your doctor may recommend prolonging the dosing interval.

Swallow the tablet with a sufficient amount of liquid (preferably with a glass of water). Food delays the absorption of tramadol/dexketoprofen; take the tablet at least 30 minutes before meals for faster action.

The score line is to help break the tablet if you have difficulty swallowing it whole.

If you take more Tramadol/Dexketoprofen Krka than you should

If you have taken too much medication, inform your doctor immediately or go to the emergency department of your nearest hospital or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount taken. Please remember to always carry the medication package or this leaflet with you.

The symptoms of overdose of this medication are:

• Vomiting, loss of appetite, stomach pain, drowsiness, dizziness/vertigo sensation, disorientation, headache (due to dexketoprofen),
• Pupil contraction, vomiting, heart failure, loss of consciousness, convulsions, and breathing difficulties (due to tramadol).

If you forget to take Tramadol/Dexketoprofen Krka

Do not take a double dose to make up for forgotten doses. Take the next dose when it is due (according to section 3 "How to take Tramadol/Dexketoprofen Krka").

If you stop treatment with Tramadol/Dexketoprofen Krka

Generally, no after-effects are expected after stopping treatment with tramadol/dexketoprofen.

However, in rare cases, patients who have been taking tramadol/dexketoprofen tablets for some time may feel unwell if they stop taking it suddenly. They may feel agitation, anxiety, nervousness, or tremors, confusion, hyperactivity, have difficulty sleeping, and gastrointestinal or stomach disorders. Rarely, people may suffer from panic attacks, hallucinations, delirium, paranoia, or feel a loss of identity. They may experience unusual perceptions such as itching, tingling, and numbness, ringing in the ears (tinnitus). Very rarely, other unusual symptoms such as confusion, delirium, feeling of being detached from oneself (depersonalization), change in perception of reality (derealization), illusions of persecution (paranoia) have been observed. Please consult your doctor if you experience any of these effects after stopping tramadol/dexketoprofen.

If you have any other questions about the use of this medication, ask your doctor.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Possible side effects are listed below according to their likelihood of occurrence.

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

Stop using tramadol/dexketoprofen if you experience a skin rash, or any lesion inside the mouth or on the mucous membranes, or any sign of allergy.

Very common(may affect more than 1 in 10 people):

• Nausea/discomfort,
• Dizziness.

Common(may affect up to 1 in 10 people):

• Vomiting,
• Stomach pain,
• Diarrhea,
• Digestive problems,
• Headache,
• Drowsiness, fatigue,
• Constipation,
• Dry mouth,
• Increased sweating.

Uncommon(may affect up to 1 in 100 people):

• Increased platelet count,
• Effects on the heart and circulation (strong heartbeat, fast heartbeat, feeling of fainting or collapse), low blood pressure. These side effects may appear especially when patients are in a vertical position or under physical stress.
• High blood pressure or very high blood pressure,
• Laryngeal inflammation (laryngeal edema),
• Low potassium levels in the blood,
• Psychotic disorders,
• Inflammation around the eyes,
• Shallow or slow breathing,
• Feeling of discomfort,
• Blood in urine,
• Feeling of spinning movement,
• Difficulty sleeping or insomnia,
• Nervousness/anxiety,
• Hot flashes,
• Flatulence,
• Fatigue,
• Pain,
• Feeling of fever or chills, general feeling of discomfort,
• Altered blood test results,
• Feeling of urge to vomit (nausea),
• Feeling of pressure or swelling in the stomach,
• Stomach inflammation,
• Skin reactions (e.g., itching, rash),
• Facial swelling.

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

• Inflammation of the lips and throat,
• Peptic ulcer, perforation of peptic ulcer, or bleeding, which may manifest with vomiting blood or black stools,

• Prostate disorders,
• Liver inflammation (hepatitis), liver damage,
• Acute kidney failure,
• Slow heartbeat,
• Seizures,
• Allergic/anaphylactic reactions (e.g., difficulty breathing, wheezing, skin inflammation) and shock (sudden circulatory failure),
• Transient loss of consciousness (syncope),
• Hallucinations,
• Fluid retention and swelling of ankles,
• Loss of or changes in appetite,
• Acne,
• Lower back pain,
• Frequent or less frequent urination than usual, with difficulty or pain,
• Menstrual disorders,
• Abnormal sensations (e.g., itching, tingling, loss of sensation),
• Tremors, muscle spasms, uncoordinated movements, muscle weakness,
• Confusion,
• Sleep disorders and nightmares,
• Perception disorders,

• Blurred vision, pupil contraction,
• Shortness of breath.

Psychological side effects may appear after treatment with tramadol/dexketoprofen. The intensity and nature of these may change (depending on the patient's personality and treatment duration):

• Mood changes (mainly euphoria and occasionally irritation),
• Changes in activity (slowing down, although sometimes increased activity),
• Loss of consciousness,
• Loss of decision-making ability, which may cause errors in judgment.

Cases of worsening asthma have been reported.

Withdrawal symptoms may appear when treatment is stopped suddenly (see "If you stop treatment with Tramadol/Dexketoprofen Krka").

Cases of seizures have been reported, mainly when administering high doses of tramadol or when tramadol is taken together with other medications that may cause them.

Very rare(may affect up to 1 in 10,000 people):

• Pancreatitis,
• Kidney problems,
• Decreased white blood cell count (neutropenia),
• Decreased platelet count in blood (thrombocytopenia),
• Ulcers on the skin, mouth, eyes, and genital areas (Stevens-Johnson syndrome and Lyell syndrome),
• Difficulty breathing due to narrowing of the airways,
• Ringing in the ears (tinnitus),
• Sensitive skin,
• Sensitivity to light.

Frequency not known(frequency cannot be estimated from the available data):

• Serotonin syndrome, which may manifest through 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 stiffness, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "what you need to know before taking Tramadol/Dexketoprofeno Krka"),
• Speech disorders,
• Extreme pupil dilation,

• Decreased blood sugar levels,
• Hypo.

Tell your doctor immediately if you notice any gastrointestinal side effects at the start of treatment (e.g., stomach pain or burning, or bleeding), if you have previously suffered from these side effects due to prolonged treatment with anti-inflammatory medications, and especially if you are an elderly patient.

The most common side effects during treatment with tramadol/dexketoprofen are nausea and dizziness, which affect more than 1 in 10 patients.

During treatment with NSAIDs, cases of fluid retention and swelling (especially in ankles and legs), increased blood pressure, and heart failure have been reported.

Medications like tramadol/dexketoprofen may be associated with a small increased risk of suffering a heart attack or stroke.

In patients with immune system disorders affecting connective tissue (systemic lupus erythematosus or mixed connective tissue disease), anti-inflammatory medications can rarely cause fever, headache, and neck stiffness.

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Medication Surveillance System for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Tramadol/Dexketoprofen Krka

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the packaging after CAD. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature.

Keep in the original packaging to protect from light and moisture.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Packaging composition and additional information

Composition of Tramadol/Dexketoprofen Krka

• The active ingredients are tramadol hydrochloride and 25 mg of dexketoprofen. Each film-coated tablet contains 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen (as dexketoprofen trometamol).

• The other components (excipients) are microcrystalline cellulose (E460), sodium croscarmellose (E468), anhydrous colloidal silica (E551), and magnesium stearate (E470b) in the tablet core; and poly(vinyl alcohol) (E1203), macrogol 3350 (E1521), titanium dioxide (E171), and talc (E553b) in the coating material. See section 2 "Tramadol/Dexketoprofen Krka contains sodium".

Appearance of the product and packaging content

The tablets are white or almost white, oval, biconvex, film-coated, scored on one side of the tablet, and marked with a K on the other side. Tablet dimensions: approximately 13 mm x 8 mm.

The score line is only to help break the tablet and facilitate swallowing, but not to divide into equal doses.

Tramadol/Dexketoprofen Krka is available in packages of:

• 10, 15, 20, 30, or 50 film-coated tablets in blisters,
• 10 x 1, 15 x 1, 20 x 1, 30 x 1, or 50 x 1 film-coated tablets in precut unit-dose blisters.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

KRKA, d.d., Novo mesto,

Šmarješka cesta 6, 8501 Novo mesto,

Slovenia

You can request more information about this medication from the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L.,

Calle de Anabel Segura 10, 28108 Alcobendas, Madrid,

Spain

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

Date of the last revision of this leaflet:January 2025

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