TAKUDEX 75 MG/25 MG ORAL SOLUTION GRANULES

Introduction

Leaflet: information for the user

Takudex 75 mg/25 mg granules for oral solution in sachet

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

1. What is Takudex and what is it used for

Takudex 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).

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

2. What you need to know before you take Takudex

Do not take Takudex

• if you are allergic to dexketoprofen, tramadol hydrochloride 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 asthma or have suffered from asthma attacks, acute allergic rhinitis (a short period of inflammation of the nasal mucosa), nasal polyps (fleshy growths in the nasal passages due to allergy), urticaria (skin 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 suffered from photoallergic or phototoxic reactions (a special form of redness or sunburn of the skin exposed to sunlight) during the intake of ketoprofen (an NSAID) or fibrates (medicines used to reduce blood fat levels)
  • if you have peptic ulcer, stomach or intestinal bleeding or if you have suffered from 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 or other active bleeding
• 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 medication (see "Use of Takudex with other medications")
• if you have epilepsy or suffer from convulsive seizures, as 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 Takudex:

• 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 suffered from any of these diseases in the past;
• if you are taking diuretics (substances that increase urine production);

• 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 your doctor about this treatment. Medications like this may be associated with a small increased risk of suffering from heart attacks (myocardial infarction) or stroke. Any risk is more likely to occur when high doses and prolonged treatments are used. Do not exceed the recommended dose or treatment duration;
• if you are an elderly patient: you may experience 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 medication 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 suffer from a disorder that affects blood production and blood cells;
• if you have systemic lupus erythematosus or mixed connective tissue disease (diseases of the immune system that affect connective tissue);
• if you have suffered from chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the past;
• if you suffer from or have suffered from stomach or intestinal disorders in the past;
• if you have an infection; see the "Infections" heading below;
• if you are taking other medications that increase the risk of peptic ulcer or bleeding, such as 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 medication: it may be that your doctor prescribes an additional medication to protect your stomach
• if you suffer from depression and are taking antidepressants, as some may interact with tramadol (see "Other medications and Takudex").
• if you are taking other medications that contain the same active substances as this medication, 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 have porphyria.

Tramadol can cause physical and psychological dependence. When tramadol 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 medications or those with drug dependence, treatment with Takudex should only be carried out for short periods and under strict medical control.

Inform your doctor if any of these problems occur during treatment with Takudex or if they occurred in the past.

Talk to your doctor if you experience any of the following symptoms while taking Takudex: extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. This may indicate that you have adrenal insufficiency (low cortisol levels). If you experience any of these symptoms, inform your doctor, who will decide whether 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 in different ways. In some people, sufficient pain relief may not be achieved, while others are more likely to experience serious side effects. If you notice any of the following side effects, you should stop taking this medication 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 monotherapy. Consult a doctor immediately if you experience any of the symptoms associated with this serious syndrome (see section 4 "Possible side effects").

Respiratory disorders related to sleep

Takudex may cause sleep-related respiratory disorders such as central sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels). These symptoms can be pauses in breathing during sleep, nocturnal awakenings 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

Takudex may mask the signs of an infection, such as pain. Consequently, Takudex 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 medication while having 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 medication.

Children and adolescents

This medication has not been studied in children or adolescents. Therefore, safety and efficacy have not been established, and the medication 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.

Use of Takudex with other medications

Inform your doctor if you are using, have recently used, or may need to use any other medication, including those obtained without a prescription. There are some medications 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 Takudex, you are taking any of the following medications:

Associations with Takudex not recommended:

• Acetylsalicylic acid, corticosteroids, or other anti-inflammatory medications
• Warfarin, heparin, or other medications 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 and other sulfonamides
• Monoamine oxidase inhibitors (MAOIs) (medications for the treatment of depression).

Associations with Takudex that require caution:

• ACE inhibitors, diuretics, 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
• Sulfonylureas such as chlorpropamide and glibenclamide, used for diabetes
• Aminoglycoside antibiotics, used to treat bacterial infections.
• The concomitant use of Takudex and sedative medications such as benzodiazepines or related medications 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 Takudex along with sedative medications, the dose and treatment duration should be limited. Inform your doctor about all sedative medications you are taking and carefully follow the recommended dose prescribed 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.

Associations with Takudex to be taken into account:

• 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 medications; i.e., medications 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.

Betablockers used for high blood pressure and heart problems.

The analgesic effect of tramadol may be reduced and the duration of action decreased if you also take medications 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 medication for cough), or alcohol while taking Takudex. You may feel drowsy or feel like you could faint. Consult your doctor if this occurs.
• if you are taking medications that can cause seizures (attacks), such as certain antidepressants or antipsychotics. The risk of having a seizure may increase if you take Takudex at the same time. Your doctor will inform you if Takudex is suitable for you.
• if you are taking certain antidepressants. Takudex may interact with these medications, and you may experience a serotonin syndrome (see section 4 "Possible side effects").
• • if you take anticoagulants (medications to thin the blood), e.g., warfarin, along with this medication. The effect of these medications may affect blood coagulation and may cause bleeding.

Taking Takudex with alcohol

Do not drink alcohol during treatment with Takudex, as it may increase the effect of the medication.

For instructions on how to take Takudex, see section 3.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

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 lead to 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 Takudex is contraindicated during pregnancy and breastfeeding.

Driving and using machines

Takudex may affect your ability to drive and use machines, as it can cause dizziness, blurred vision, or drowsiness as side effects of treatment. This occurs mainly when Takudex is taken with medications that affect mood and emotions or when taken with alcohol.

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

3. How to Take Takudex

Follow your doctor's administration instructions for this medication exactly. If in doubt, consult your doctor again.

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

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

The recommended dose is generally 1 sachet (corresponding to 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen) every 8 hours, not exceeding 3 sachets 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

Takudex 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.

Patient with Severe Hepatic or Renal Impairment/Dialysis:

If you have severe hepatic impairment and/or moderate to severe renal impairment, you should not take Takudex.

If you have renal dysfunction, if in your case the impairment is mild, your doctor may recommend prolonging the dosing interval.

If you have hepatic dysfunction, if in your case the impairment is mild or moderate, your doctor may recommend prolonging the dosing interval.

Dissolve the entire contents of each sachet in a glass of water; shake well to help dissolve. The obtained solution should be taken immediately after reconstitution.

Food delays the absorption of Takudex; take the oral solution granule in a sachet at least 30 minutes before meals for faster action.

If You Take More Takudex 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, disorientation, headache (due to dexketoprofen).
• Pupil contraction, vomiting, heart failure, loss of consciousness, convulsions, and difficulty breathing (due to tramadol).

If You Miss a Dose of Takudex

Do not take a double dose to make up for missed doses. Take the next dose when scheduled (according to section 3 "How to Take Takudex").

If You Stop Treatment with Takudex

Generally, no after-effects are expected after stopping treatment with Takudex.

However, in rare cases, patients who have been taking Takudex 75 mg/25 mg oral solution granule in a sachet 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, or 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), persecution illusions (paranoia) have been observed. Please consult your doctor if you experience any of these effects after stopping Takudex.

If you have any other doubts 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 detailed 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 Takudex if you experience a skin rash, any lesion inside the mouth or on the mucous membranes, or any sign of allergy.

Very Common Side Effects (may affect more than 1 in 10 people):

• Nausea/discomfort
• Dizziness

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

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

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

• Increased platelet count
• Effects on the heart and blood 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 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
• 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 nausea (retching)
• Feeling of pressure or swelling in the stomach
• Stomach inflammation
• Skin reactions (e.g., itching, rash)
• Facial swelling

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

• Inflammation of the lips and throat
• Peptic ulcer, peptic ulcer perforation, or bleeding, which may manifest with vomiting blood or black stools
• Prostate disorders
• Hepatitis (liver inflammation), 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 or changes in appetite
• Acne
• Lower back pain
• Frequent or less frequent urination than normal, with difficulty or pain.
• Menstrual disorders
• Abnormal sensations (e.g., itching, tingling, numbness)
• 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 occur after treatment with Takudex. 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.

Signs of withdrawal may appear when treatment is stopped suddenly (see "If you stop treatment with Takudex").

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 blood cell count (neutropenia)
• Decreased platelet count in blood (thrombocytopenia)
• Skin, mouth, eye, or genital ulcers (Stevens-Johnson syndrome and Lyell syndrome). Difficulty breathing due to narrowing of the airways
• Ringing in the ears (tinnitus)
• Sensitive skin
• Sensitivity to light

Unknown Frequency (cannot be estimated from available data)

• Serotonin syndrome, which may manifest as changes in mental state (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 Takudex").

• Speech disorders
• Extreme pupil dilation
• Decreased blood sugar levels
• Hiccup

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 experienced any of these side effects due to prolonged treatment with anti-inflammatory drugs, and especially if you are an elderly patient.

The most common side effects during treatment with Takudex 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 Takudex may be associated with a small increased risk of having a heart attack or stroke.

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

Reporting Side Effects

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

5. Storage of Takudex

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date stated on the packaging and on the sachet 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.

Medications should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medication in the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Takudex Composition:

• The active ingredients are tramadol hydrochloride and dexketoprofen. Each sachet contains: 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen (as dexketoprofen trometamol).
• The other ingredients are: sucrose, lemon flavor, and acesulfame potassium (E-950).

Product Appearance and Package Contents:

White or almost white oral solution granule, presented in sachets formed by a multilayer thermosealed laminate of paper-aluminum-polyethylene (as a copolymer with vinyl acetate) in a cardboard box.

Takudex is available in packages of 2, 3, 10, 15, 20, 100, and 500 sachets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder

GUIDOTTI FARMA, S.L.

Alfonso XII, 587 - Badalona (Barcelona)

Spain

Manufacturer

E-Pharma Trento S.p.A.

Frazione Ravina – Via Provina, 2

Trento, 38123

Italy

This medication is authorized in the Member States of the European Economic Area under the following names:

Italy: Dextradol

Spain: Takudex

Date of the Last Revision of this Leaflet: December 2022

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/