Skudexa

Package Leaflet: Information for the Patient

Skudexa, 75 mg + 25 mg, Granules for Oral Solution

Tramadol Hydrochloride + Dexketoprofen

Read the Package Leaflet Carefully Before Taking the Medication Because it Contains Important Information for the Patient.

• 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor (see section 4).

Contents of the Package Leaflet:

• 1. What is Skudexa and What is it Used For
• 2. Important Information Before Taking Skudexa
• 3. How to Take Skudexa
• 4. Possible Side Effects
• 5. How to Store Skudexa
• 6. Contents of the Package and Other Information

1. What is Skudexa and What is it Used For

Skudexa contains tramadol hydrochloride and dexketoprofen as active substances.
Tramadol hydrochloride is a pain reliever belonging to the group of medicines called opioids, which 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 medicines called nonsteroidal anti-inflammatory drugs (NSAIDs).
Skudexa is used for the symptomatic short-term treatment of moderate to severe acute pain in adults.

2. Important Information Before Taking Skudexa

When Not to Take Skudexa:

• if you are allergic to dexketoprofen, tramadol hydrochloride, or any of the other ingredients of this medicine (listed in section 6)
• if you have a hypersensitivity to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs)
• if you have had asthma attacks, acute allergic rhinitis (short-term inflammation of the nasal mucosa), nasal polyps (growths in the nose caused by allergies), hives (rash on the skin), angioedema (swelling of the face, eyes, lips, tongue, or respiratory distress) or wheezing after taking acetylsalicylic acid or another NSAID
• if you have had photoallergic or phototoxic reactions (in the form of redness and/or blisters on the skin exposed to the sun) when taking ketoprofen (NSAID) or fibrates (medicines used to lower blood lipid levels)
• if you have stomach or duodenal ulcer disease or bleeding from the stomach or intestines, or if you have had bleeding from the stomach or intestines, ulcers, or perforation, including cases due to previous intake of NSAIDs
• if you have chronic gastrointestinal problems (e.g., indigestion, heartburn)
• if you have intestinal diseases with chronic inflammation (Crohn's disease or ulcerative colitis)
• if you have severe heart failure, moderate or severe kidney or liver function disorders
• if you have an increased tendency to bleed, coagulation disorders, or other active bleeding
• if you are severely dehydrated (excessive fluid loss from the body) due to vomiting, diarrhea, or inadequate fluid intake
• in case of acute alcohol poisoning, sleeping pills, painkillers, or medications that affect mood and emotions
• if you are taking monoamine oxidase inhibitors (MAOIs) (certain medications used to treat depression) or have taken them within the last 14 days before starting treatment with this medication (see "Skudexa and Other Medicines")
• if you have epilepsy or have had seizures, as the risk of seizures may increase
• if you have difficulty breathing
• if you are pregnant or breastfeeding.

Warnings and Precautions

Before starting treatment with Skudexa, discuss the following with your doctor:

• if you have an allergy or have had allergy problems in the past
• if you have kidney, liver, or heart problems (hypertension and/or heart failure) as well as fluid retention or if any of the above problems have occurred in the past
• if you are taking diuretics (substances that increase urine production)
• if you have heart problems, have had a stroke, or are suspected to be at risk for these conditions (e.g., due to high blood pressure, diabetes, high cholesterol, or smoking). In such cases, consult your doctor before taking the medication; taking such medications as Skudexa may be associated with a slight increase in the risk of heart attack ("myocardial infarction") or stroke. This risk increases with long-term use of high doses of the medication. Do not exceed the recommended dose and duration of treatment
• if you are elderly: there is an increased risk of side effects (see section 4). In this case, consult your doctor immediately
• if you are a woman with fertility problems: this medication may interfere with female fertility and is not recommended for women planning pregnancy or being treated for infertility
• if you have blood disorders or blood cell disorders
• if you have systemic lupus erythematosus or mixed connective tissue disease (immune system disorders affecting connective tissue)
• if you have had chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) in the past
• if you have other stomach or intestinal diseases
• if you have an infection - see below, section titled "Infections"
• if you are taking other medications that increase the risk of stomach ulcers and/or duodenal ulcers or bleeding, such as oral steroids, certain antidepressants (SSRI, i.e., selective serotonin reuptake inhibitors), medications that prevent blood clots, such as acetylsalicylic acid or anticoagulants, such as warfarin. In such cases, consult your doctor before taking the medication, who may decide to administer an additional medication with a protective mechanism
• if you have depression and are taking antidepressants, as some of them may interact with tramadol (see "Skudexa and Other Medicines")
• if you are taking other medications containing the same active substances, do not exceed the maximum daily dose of dexketoprofen or tramadol
• if you think you are dependent on other painkillers (opioids)
• if you have impaired consciousness (if you feel like you might faint)
• if you are in shock (cold sweat may be a sign of this condition)
• if you have increased intracranial pressure (e.g., due to head injury or brain disease)
• if you have difficulty breathing
• if you have porphyria (a disease characterized by disorders of heme metabolism).

Tramadol may lead to physical and psychological dependence. If the medication is taken for a long time, its effect may weaken, and higher doses may be needed (development of tolerance). In patients with a tendency to abuse medications or those dependent on medications, treatment with Skudexa should be short-term and under close medical supervision.
Tell your doctor if any of these problems occur during treatment with Skudexa or have occurred in the past.
If you experience any of the following symptoms while taking Skudexa, tell your doctor: excessive 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 such symptoms occur, consult your doctor, who will decide whether you need hormone replacement therapy.
Tramadol is metabolized in the liver by an enzyme. In some people, there is a certain variant of this enzyme, which can have different effects. In some people, pain relief may not be sufficient, and in others, the risk of serious side effects may be higher.
Stop taking the medication and consult your doctor immediately if you experience any of the following side effects: slowed breathing or shallow breathing, confusion, drowsiness, pinpoint pupils, nausea, or vomiting, constipation, loss of appetite.
After taking tramadol in combination with certain antidepressants or tramadol alone, there is a small risk of serotonin syndrome. If you experience any symptoms of this syndrome with a severe course, seek medical attention immediately (see section 4 "Possible Side Effects").

Respiratory Depression During Sleep

Skudexa may cause respiratory depression during sleep, 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 you or someone else observes these symptoms, consult your doctor. Your doctor may recommend reducing the dose.

Infections

Skudexa may mask the symptoms of infection, such as fever and pain. As a result, Skudexa may delay the application of appropriate infection treatment and consequently lead to increased risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you are taking this medication during an infection, and the symptoms of the infection persist or worsen, consult your doctor immediately.
Avoid taking this medication during chickenpox.

Children and Adolescents

This medication has not been studied in children and adolescents. The safety and efficacy of this medication have not been established, and therefore, it should not be used in children and adolescents.
Use in children with respiratory disorders
Tramadol is not recommended in children with respiratory disorders, as the symptoms of tramadol toxicity may be exacerbated in them.

Skudexa and Other Medicines

Tell your doctor about all the medications you are currently taking or have recently taken, as well as any medications you plan to take, including those available without a prescription.
Certain medications should not be taken at the same time as Skudexa, and for others, the dose may need to be changed due to concurrent use of Skudexa.
Always inform your doctor if you are taking any of the following medications with Skudexa:
Concomitant use not recommended:

• Acetylsalicylic acid, corticosteroids, or other anti-inflammatory medications
• Warfarin, heparin, or other anticoagulant medications
• Lithium used to treat certain mood disorders
• Methotrexate used to treat rheumatoid arthritis and cancer
• Hydantoin derivatives and phenytoin used to treat epilepsy
• Sulfamethoxazole used to treat bacterial infections and other sulfonamides
• Monoamine oxidase inhibitors (MAOIs) (medications used to treat depression).

Concomitant use requiring caution:

• ACE inhibitors, diuretics, angiotensin II antagonists used to treat high blood pressure and heart disease
• Pentoxifylline used to treat ulcers in chronic venous insufficiency
• Zidovudine used to treat viral infections
• Sulfonylurea derivatives such as chlorpropamide and glibenclamide used to treat diabetes
• Aminoglycoside antibiotics used to treat bacterial infections.
• Concomitant use of Skudexa with sedative medications, such as benzodiazepines or other medications with similar effects to benzodiazepines, may increase the risk of sedation, respiratory depression, coma, and may be life-threatening. Therefore, concomitant use should only be considered when other treatment options are not possible. If your doctor prescribes Skudexa for concomitant use with sedative medications, the dose and duration of treatment should be limited by your doctor. Inform your doctor about all sedative medications you are taking and follow your doctor's instructions carefully. It may be helpful to inform friends and family members that such symptoms may occur. Consult your doctor if such symptoms occur.

Concomitant use requiring special consideration:

• Quinolone antibiotics (e.g., ciprofloxacin, levofloxacin) used to treat bacterial infections
• Cyclosporine and tacrolimus used to treat immune system disorders and transplants
• Streptokinase and other thrombolytic or fibrinolytic medications, i.e., medications used to dissolve blood clots
• Probenecid used to treat gout
• Digoxin used to treat chronic heart failure
• Mifepristone used as an abortion pill
• Antidepressant medications from the selective serotonin reuptake inhibitor (SSRI) class
• Antiplatelet medications used to reduce platelet aggregation and blood clot formation
• Tenofovir, deferiprone, pemetrexed
• Beta-blockers used to treat high blood pressure and heart disease

The pain-relieving effect of tramadol may be reduced, and the duration of action may be shortened when you are also taking:

• Carbamazepine (for seizure disorders)
• Buprenorphine, nalbuphine, or pentazocine (pain medications)
• Ondansetron (prevents nausea).

The risk of side effects increases:

• if you are taking sedative medications, sleeping pills, other pain medications, such as morphine and codeine (also for cough), or alcohol while taking Skudexa. You may feel drowsy or feel like you might faint. If this happens, tell your doctor
• if you are taking medications that can cause seizures (convulsions), such as certain antidepressants or antipsychotics. The risk of seizures may increase due to concomitant use of Skudexa. Your doctor will decide whether Skudexa is suitable for you
• if you are taking certain antidepressants. Skudexa may interact with these medications and cause serotonin syndrome (see section 4 "Possible Side Effects")
• if you are taking anticoagulant medications (blood thinners), such as warfarin, along with this medication. The effect of these medications on blood clotting may be disrupted, and bleeding may occur.

Using Skudexa with Alcohol

Do not drink alcohol while taking Skudexa, as it may enhance the effect of the medication.
Instructions for taking Skudexa - see section 3.

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor for advice before taking this medication.
Dexketoprofen may cause kidney and heart problems in the unborn baby.
This medication may increase the risk of bleeding in you and your baby and may cause delayed or prolonged labor.
From the 20th week of pregnancy, dexketoprofen may cause:

• kidney problems in the unborn baby - this may lead to a decrease in the amount of amniotic fluid surrounding the baby (oligohydramnios)
• narrowing of a blood vessel (ductus arteriosus) in the baby's heart.

Tramadol is excreted into breast milk.
Taking Skudexa is contraindicated during pregnancy and breastfeeding.

Driving and Using Machines

Skudexa may affect your ability to drive and use machines, due to the possibility of dizziness, vision disturbances, or drowsiness as side effects during treatment.
This is especially true when Skudexa is taken with medications that affect mood and emotions or with alcohol.
If you experience such symptoms, do not drive vehicles or operate machinery until the symptoms have resolved.

Skudexa Contains Sucrose

Skudexa contains 2.7 g of sucrose per dose. This should be taken into account in patients with diabetes.
If your doctor has informed you that you have an intolerance to some sugars, consult your doctor before taking the medication.

3. How to Take Skudexa

Always take this medication exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Use the smallest effective dose for the shortest duration necessary to relieve the symptoms. If the symptoms of the infection (such as fever and pain) persist or worsen, consult your doctor immediately (see section 2).
The dose of Skudexa will depend on the type, severity, and duration of the pain.
Your doctor will tell you how many sachets to take per day and for how long.
The recommended daily dose is usually 1 sachet (corresponding to 75 mg tramadol hydrochloride and 25 mg dexketoprofen) every 8 hours, with no more than 3 sachets per day (corresponding to 225 mg tramadol hydrochloride and 75 mg dexketoprofen), and treatment should not last longer than 5 days.

Use in Children and Adolescents

Skudexa should not be used in children and adolescents.

Elderly Patients

In patients aged 75 or older, your doctor may recommend longer intervals between doses, as the body may metabolize the medication more slowly.

Patients with Severe Liver or Kidney Disease (Failure)/Dialysis Patients

Patients with severe liver and/or kidney disease should not take Skudexa.
In case of kidney function disorders, if you have mild kidney failure, your doctor may recommend prolonging the interval between doses.
In case of liver function disorders, if you have mild or moderate liver failure, your doctor may recommend prolonging the interval between doses.
The contents of the sachet should be dissolved in a glass of water, mixed well to facilitate dissolution.
The resulting solution should be drunk immediately after preparation.
Food delays the absorption of Skudexa, so to achieve a faster effect, take the granules for oral solution in sachets at least 30 minutes before a meal.

Overdose of Skudexa

If you have taken more than the recommended dose of Skudexa, inform your doctor or go to the emergency department of the nearest hospital immediately. Remember to take the package or patient information leaflet with you.
Symptoms of overdose are:

• vomiting, loss of appetite, abdominal pain, drowsiness, dizziness/spinning sensation, disorientation, headache (due to dexketoprofen)
• pupil constriction, vomiting, heart failure, loss of consciousness, seizures, and breathing difficulties (due to tramadol).

Missing a Dose of Skudexa

Do not take a double dose to make up for a missed dose. The next dose should be taken according to the dosing schedule (see section 3 "How to Take Skudexa").

Stopping Skudexa Treatment

It is unlikely that you will experience any effects from stopping Skudexa treatment.
However, in rare cases, patients who have taken Skudexa for some time may feel unwell if treatment is stopped abruptly. They may feel agitated, anxious, nervous, or unsure, feel confused, overexcited, have sleep problems, and have stomach or intestinal disorders. Rarely, patients may experience panic attacks, hallucinations, delusions, paranoia, or loss of identity. They may experience unusual sensations, such as itching, tingling, numbness, and ringing in the ears. Further unusual symptoms, such as confusion, delusions, depersonalization, and changes in perception of reality (derealization) and persecutory delusions (paranoia), have been observed very rarely. If you experience any of these symptoms after stopping Skudexa treatment, consult your doctor.
If you have any further questions about taking this medication, ask your doctor.

4. Possible Side Effects

Like all medicines, Skudexa can cause side effects, although not everybody gets them.
Possible side effects are listed below and are grouped by frequency of occurrence.
Inform your doctor immediately if you experience symptoms of an allergic reaction, such as swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives with breathing difficulties.
Stop taking Skudexa as soon as possible if you notice the appearance of a rash or any changes in the mouth or mucous membranes or any signs of allergy.
Very Common Side Effects(may affect more than 1 in 10 people):

• nausea
• dizziness.

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

• vomiting
• abdominal pain
• diarrhea
• indigestion
• headache
• drowsiness, fatigue
• constipation
• dry mouth
• excessive sweating.

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

• increased platelet count
• effects on the heart and blood vessels (palpitations, rapid heartbeat, feeling of fainting or collapse), low blood pressure. These side effects may occur especially when you are in an upright position or during physical exertion.
• high or very high blood pressure
• swelling of the vocal cords (laryngeal edema)
• decreased potassium levels in the blood
• psychotic disorders
• swelling around the eyes
• shallow or slow breathing
• discomfort, feeling unwell
• blood in the urine
• feeling of spinning
• insomnia or sleep disturbances
• anxiety/nervousness
• hot flashes
• bloating
• fatigue
• pain
• feeling of fever and chills, general malaise
• abnormal blood test results
• nausea (vomiting reflex)
• feeling of pressure in the stomach, bloating
• gastritis
• skin reactions (e.g., itching, rash)
• swelling of the face.

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

• swelling of the lips and throat
• stomach or duodenal ulcer disease and/or bleeding, which may manifest as bloody vomiting or black stools
• prostate disorders
• hepatitis (liver inflammation), liver damage
• acute kidney failure
• slow heartbeat
• seizures
• allergic reactions/anaphylaxis (e.g., difficulty breathing, wheezing, skin swelling) and shock (sudden circulatory failure)
• transient loss of consciousness (fainting)
• hallucinations
• water retention or swelling of the ankles
• loss of appetite, changes in appetite
• acne
• back pain
• frequent urination or less than usual, with difficulty or pain
• menstrual disorders
• sensory disturbances (e.g., itching, tingling, numbness)
• tremors, muscle spasms, uncoordinated movements, weak muscles
• confusion
• sleep disturbances and nightmares
• perception disorders
• blurred vision, pinpoint pupils
• shortness of breath.

The medication may cause psychological disturbances. Their intensity and nature may vary (depending on the patient's personality and the duration of treatment) and include:

• mood changes (mostly good mood, sometimes irritability)
• changes in activity (slowing down, but sometimes increased activity)
• feeling less aware
• being less able to make decisions, which may lead to errors in reasoning.

Asthma has been reported to worsen.
Upon sudden discontinuation of treatment, withdrawal symptoms may occur (see "Stopping Skudexa Treatment").
Seizures have occurred mainly after administration of high doses of tramadol or when tramadol was used at the same time as other medications that can cause seizures.
Very Rare Side Effects(may affect up to 1 in 10,000 people):

• pancreatitis
• kidney problems
• decreased white blood cell count (neutropenia)
• decreased platelet count (thrombocytopenia)
• ulcers of the skin, lips, eyes, and genital areas (Stevens-Johnson syndrome and Lyell's syndrome)
• breathing difficulties due to bronchospasm
• ringing in the ears (tinnitus)
• skin hypersensitivity
• hypersensitivity to light.

Frequency Not Known(frequency cannot be estimated from the available data):

• serotonin syndrome, whose symptoms may include 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 stiffness, and lack of coordination, and symptoms from the gastrointestinal tract (e.g., nausea, vomiting, diarrhea) (see section 2 "Important Information Before Taking Skudexa")
• speech disorders
• extreme pupil dilation
• low blood sugar
• hiccups.

Tell your doctor if you notice any side effects, including those not listed in this leaflet, or if you experience any side effects not listed in this leaflet.
The most common side effects during treatment with Skudexa are nausea and dizziness, which occur in more than 1 in 10 patients.
When taking nonsteroidal anti-inflammatory medications, fluid retention and swelling (especially of the ankles and feet) may occur, as well as increased blood pressure and heart failure.
Taking medications like Skudexa may be associated with a slight increase in the risk of heart attack ("myocardial infarction") or stroke.
In patients with immune system disorders affecting connective tissue (systemic lupus erythematosus or mixed connective tissue disease), taking anti-inflammatory medications may rarely cause fever, headache, and stiffness of the neck/cervical spine.

Reporting Side Effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist.
Side effects can be reported directly to the Department of Post-Marketing Surveillance of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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.
Reporting side effects will help to gather more information on the safety of the medication.

5. How to Store Skudexa

Keep this medication out of the sight and reach of children.
Do not use this medication after the expiry date stated on the carton and sachet after "EXP". The expiry date refers to the last day of the month.
There are no special storage temperature requirements.
Store in the original package to protect from light.
Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Contents of the Package and Other Information

What Skudexa Contains

• The active substances of Skudexa are tramadol hydrochloride and dexketoprofen. Each sachet contains 75 mg tramadol hydrochloride and 25 mg dexketoprofen (in the form of dexketoprofen trometamol).
• Other ingredients are: sucrose, lemon flavor, acesulfame potassium (E 950).

What Skudexa Looks Like and Contents of the Package

White to almost white granules for oral solution, available in heat-sealed sachets made of multilayer foil Paper/Aluminum/PE (in the form of a vinyl acetate copolymer) in a cardboard box.
Packages contain 2, 3, 10, 15, 20, 50, 100, and 500 sachets.
Not all pack sizes may be marketed.

Marketing Authorization Holder

Menarini International Operations Luxembourg S.A.
1, Avenue de la Gare
1611 Luxembourg
Luxembourg

Manufacturer

E-Pharma Trento S.p.A.
Frazione Ravina – Via Provina, 2
38123 Trento (TN)
Italy
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, Greece, Hungary, Ireland, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, United Kingdom (Northern Ireland): Skudexa
France: Skudexum
Italy: Lenizak
Spain: Enanplus
Date of last revision of the leaflet: 12/2022