SKUDEXA 75 mg/25 mg Tablets

Contents of the leaflet

1. Leaflet accompanying the packaging: patient information
2. Skudexa 75 mg + 25 mg
   1. Read the leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet:
3. What is Skudexa and what is it used for
4. Important information before taking Skudexa
   1. When not to take Skudexa:
   2. Warnings and precautions
   3. Breathing difficulties during sleep
   4. Infections
   5. Children and adolescents
   6. Skudexa and other medicines
   7. Taking Skudexa with alcohol
   8. Pregnancy, breastfeeding, and fertility
   9. Driving and using machines
5. How to take Skudexa
   1. Use in children and adolescents
   2. Elderly patients
   3. Patients with severe liver or kidney disease (failure)/dialysis patients
   4. Overdose
   5. Missed dose
   6. Stopping treatment with Skudexa
6. Possible side effects
   1. Reporting side effects
7. How to store Skudexa
8. Contents of the pack and other information
   1. What Skudexa contains
   2. What Skudexa looks like and contents of the pack
   3. Marketing authorization holder
   4. Manufacturer

Leaflet accompanying the packaging: patient information

Skudexa 75 mg + 25 mg

coated tablets
Tramadol hydrochloride + Dexketoprofen

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

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor. See section 4.

Table of contents of the 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 pack 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 non-steroidal anti-inflammatory drugs (NSAIDs).
Skudexa is used for the symptomatic short-term treatment of moderate to severe acute pain in adults.
The patient should tell their doctor if they do not feel better or feel worse after taking the medicine.

2. Important information before taking Skudexa

When not to take Skudexa:

• if the patient is allergic to dexketoprofen, tramadol hydrochloride, or any of the other ingredients of this medicine (listed in section 6)
• if the patient has hypersensitivity to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs)
• if the patient has a history of asthma attacks, acute allergic rhinitis (short-term inflammation of the nasal mucosa), nasal polyps (growths in the nose caused by allergy), hives (rash on the skin), or angioedema (swelling of the face, eyes, lips, tongue, or respiratory distress) after taking acetylsalicylic acid or another NSAID
• if the patient has a history of hypersensitivity reactions to sunlight: photoallergic or phototoxic reactions (especially in the form of redness and/or blisters on the skin exposed to the sun) while taking ketoprofen (NSAID) or fibrates (medicines used to lower blood lipid levels)

blisters on the skin exposed to the sun) while taking ketoprofen (NSAID) or fibrates (medicines used to lower blood lipid levels)

• if the patient has stomach or duodenal ulcer disease or bleeding, or if they have had bleeding, ulceration, or perforation in the past, including cases due to previous NSAID use
• if the patient has chronic gastrointestinal problems (e.g., indigestion, heartburn)
• if the patient has intestinal diseases with chronic inflammation (Crohn's disease or ulcerative colitis)
• if the patient has severe heart failure, moderate or severe kidney failure, or severe liver failure
• if the patient has a tendency to bleed excessively or has coagulation disorders
• if the patient is 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 mood-altering medicines
• if the patient is also taking monoamine oxidase inhibitors (MAOIs) (certain medicines used to treat depression) or has taken them within the last 14 days before starting treatment with this medicine (see "Skudexa and other medicines")
• if the patient has epilepsy or has had seizures, as the risk of seizures may increase
• if the patient has difficulty breathing
• if the patient is pregnant or breastfeeding.

Warnings and precautions

Before starting treatment with Skudexa, the patient should discuss the following with their doctor:

• if the patient has an allergy or has had allergy problems in the past
• if the patient has kidney, liver, or heart problems (hypertension and/or heart failure), as well as fluid retention, or if any of these problems have occurred in the past
• in patients taking diuretics
• if the patient has heart problems, has had a stroke, or is suspected to be at risk for these conditions (e.g., due to high blood pressure, diabetes, high cholesterol, or smoking). In such cases, the patient should consult their doctor before taking Skudexa. Taking such medicines as Skudexa may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. This risk increases with long-term use of high doses of the medicine. The patient should not exceed the recommended dose and duration of treatment
• if the patient is elderly: there is an increased risk of side effects (see section 4). In such cases, the patient should contact their doctor immediately
• in women with fertility problems: this medicine may affect female fertility and is not recommended for women planning to become pregnant or being treated for infertility
• if the patient has blood disorders or blood cell problems
• if the patient has systemic lupus erythematosus or mixed connective tissue disease (immune system disorders affecting connective tissue)
• if the patient has had chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease) in the past
• if the patient has other stomach or intestinal diseases
• if the patient has an infection - see below, section "Infections"
• if the patient is taking other medicines 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), anticoagulant medicines such as warfarin. In such cases, the patient should consult their doctor before taking the medicine, as the doctor may decide to prescribe an additional medicine with a protective mechanism

If the patient is taking other medicines containing the same active substances, they should not exceed the maximum daily dose of dexketoprofen or tramadol.

If the patient thinks they are dependent on other painkillers (opioids)

If the patient has impaired consciousness (if the patient feels they may faint)

If the patient is in shock (cold sweat may be a sign of this condition)

If the patient has increased intracranial pressure (e.g., due to head injury or brain disease)

If the patient has breathing difficulties

If the patient has porphyria.

Tramadol may lead to physical and psychological dependence. If the medicine 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 medicines or who are dependent on medicines, treatment with Skudexa should be short-term and under close medical supervision. The patient should inform their doctor if any of these problems occur during treatment with Skudexa or have occurred in the past. If the patient experiences any of the following symptoms while taking Skudexa, they should tell their doctor: excessive tiredness, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. This may indicate that the patient has adrenal insufficiency (low cortisol levels). If such symptoms occur, the patient should contact their doctor, who will decide whether the patient needs hormone replacement. Tramadol is converted in the liver by an enzyme. In some people, there is a certain 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. The patient should stop taking the medicine and contact their doctor immediately if they experience any of the following side effects: slow 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 the patient experiences any symptoms of this syndrome with a severe course, they should immediately consult their doctor (see section 4 "Possible side effects").

Breathing difficulties during sleep

Skudexa may cause breathing difficulties 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 the patient or someone else observes these symptoms, they should contact their doctor. The doctor may recommend reducing the dose.

Infections

Skudexa may mask the symptoms of an infection, such as fever and pain. As a result, Skudexa may delay the use of appropriate infection treatment and lead to increased risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to chickenpox. If the patient is taking this medicine during an infection, and the symptoms of the infection persist or worsen, they should consult their doctor immediately. The patient should avoid taking this medicine during chickenpox.

Children and adolescents

Skudexa has not been studied in children and adolescents. The safety and efficacy of this medicine have not been established, and therefore, it should not be used in children and adolescents. Use in children with breathing difficulties Tramadol is not recommended in children with breathing difficulties, as the symptoms of tramadol toxicity may be exacerbated.

Skudexa and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, including those available without a prescription. Certain medicines should not be taken at the same time as Skudexa, and for others, the dose may need to be changed when taken with Skudexa. The patient should always inform their doctor if they are taking any of the following medicines with Skudexa:

• Acetylsalicylic acid, corticosteroids, or other anti-inflammatory medicines
• Warfarin, heparin, or other anticoagulant medicines
• 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
• Monoamine oxidase inhibitors (MAOIs) (medicines used to treat depression).

Concomitant use requiring caution:

• ACE inhibitors, diuretics, beta-blockers, and 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
• Chlorpropamide and glibenclamide used to treat diabetes
• Aminoglycoside antibiotics used to treat bacterial infections.
• Concomitant use of Skudexa with sedative medicines such as benzodiazepines or other medicines with similar effects to benzodiazepines may increase the risk of sedation, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when other treatment options are not possible. If the doctor prescribes Skudexa to be taken with sedative medicines, the dose and duration of treatment should be limited by the doctor. The patient should tell their doctor about all sedative medicines they are taking and strictly follow the doctor's instructions. It may be helpful to inform friends and family members that such symptoms may occur. The patient should contact their 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 medicines, i.e., medicines used to dissolve blood clots
• Probenecid used to treat gout
• Digoxin used to treat chronic heart failure
• Mifepristone used as an abortion pill
• Selective serotonin reuptake inhibitors (SSRIs) used to treat depression
• Antiplatelet medicines used to reduce blood clotting
• Tenofovir, deferiprone, pemetrexed

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

• Carbamazepine (for epilepsy)
• Buprenorphine, nalbuphine, or pentazocine (painkillers)
• Ondansetron (to prevent nausea)

The risk of side effects increases:

• if the patient is taking sedative medicines, sleeping pills, other painkillers, such as morphine and codeine (also for cough), or alcohol while taking Skudexa. The patient may feel drowsy or may feel faint. If this happens, the patient should tell their doctor
• if the patient is taking medicines that can cause seizures (convulsions), such as certain antidepressants or antipsychotics. The risk of seizures may increase due to concomitant use of Skudexa. The doctor will decide whether Skudexa is suitable for the patient
• if the patient is taking certain antidepressants. Skudexa may interact with these medicines and cause serotonin syndrome (see section 4 "Possible side effects")
• if the patient is taking anticoagulant medicines (blood thinners), such as warfarin, with this medicine. The effect of these medicines on blood clotting may be disrupted, and bleeding may occur.

Taking Skudexa with alcohol

The patient should not drink alcohol while being treated with Skudexa, as this may enhance the effect of the medicine. For instructions on how to take Skudexa, see section 3.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor before taking this medicine. Dexketoprofen may cause kidney and heart problems in the unborn baby. This medicine may increase the risk of bleeding in the mother and the baby and may cause delayed or prolonged labor. From the 20th week of pregnancy, dexketoprofen may cause: kidney problems in the unborn baby, which may lead to reduced amniotic fluid volume around the baby (oligohydramnios) or narrowing of the arterial duct in the baby's heart. Tramadol is excreted into breast milk. Skudexa is contraindicated in pregnancy and during breastfeeding.

Driving and using machines

Skudexa may affect the patient's ability to drive and use machines, due to possible dizziness, vision disturbances, or drowsiness as side effects during treatment. This is especially true when Skudexa is taken with medicines that affect mood and emotions or with alcohol. If the patient experiences such symptoms, they should not drive vehicles or operate machinery until the symptoms have resolved. This medicine contains less than 1 mmol (23 mg) of sodium per dose, which means it is essentially sodium-free.

3. How to take Skudexa

The patient should always take this medicine exactly as their doctor has told them. If they are not sure, they should ask their doctor. The patient should use the smallest effective dose for the shortest duration necessary to relieve symptoms. If the symptoms of an infection (such as fever and pain) persist or worsen, the patient should consult their doctor immediately (see section 2). The doctor will inform the patient about the dose of Skudexa, which will depend on the type, severity, and duration of the pain. The doctor will inform the patient about the number of tablets to take per day and the duration of treatment. The recommended daily dose is usually 1 coated tablet (corresponding to 75 mg tramadol hydrochloride and 25 mg dexketoprofen) every 8 hours. The total daily dose should not exceed 3 coated tablets (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 years or older, the doctor may recommend longer intervals between doses, as the body may metabolize the medicine 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 problems, if the patient has mild kidney failure, the doctor may recommend longer intervals between doses. In case of liver problems, if the patient has mild or moderate liver failure, the doctor may recommend longer intervals between doses. The patient should swallow the tablets with a sufficient amount of liquid (preferably a glass of water). Food delays the absorption of Skudexa, so for a faster effect, the patient should take the tablet at least 30 minutes before a meal. The score line on the tablet will help the patient break the tablet in case of difficulty swallowing it whole.

Overdose

If the patient has taken more than the recommended dose of Skudexa, they should immediately inform their doctor or go to the emergency department of the nearest hospital. The patient should remember to take the package or patient information leaflet with them. Symptoms of overdose include: nausea, loss of appetite, abdominal pain, drowsiness, dizziness/spinning sensation, disorientation, headache (due to dexketoprofen), and pinpoint pupils, vomiting, heart failure, loss of consciousness, seizures, and breathing difficulties (due to tramadol).

Missed dose

The patient should 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 treatment with Skudexa

The patient should not expect any consequences after stopping treatment with Skudexa. 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 insecure, confused, restless, sleep disturbances, and gastrointestinal 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 paranoid delusions, have been observed very rarely. If the patient experiences any of these symptoms after stopping treatment with Skudexa, they should consult their doctor. If the patient has any further doubts about taking this medicine, they should consult their doctor.

4. Possible side effects

Like all medicines, Skudexa can cause side effects, although not everybody gets them. The possible side effects are listed below and are grouped by how common they are:

• 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 the patient is in an upright position or during physical exertion.
• high or very high blood pressure
• swelling of the vocal cords (laryngeal edema)
• low potassium levels in the blood
• psychotic disorders
• swelling around the eyes
• shallow or slow breathing
• discomfort, feeling abnormal
• blood in the urine
• spinning sensation
• insomnia or sleep disturbances
• nervousness/anxiety
• 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, perforation, or bleeding, which may manifest as bloody vomiting or black stools
• prostate problems
• liver inflammation (hepatitis), 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
• fluid 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.

Psychological side effects may occur after treatment with Skudexa. 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 cessation of treatment, withdrawal symptoms may occur (see "Stopping treatment with Skudexa"). Seizures have mainly occurred after administration of high doses of tramadol or when tramadol was used at the same time as other medicines that may cause seizures. Very rare side effects(may affect up to 1 in 10,000 people):

• pancreatitis
• kidney problems
• low white blood cell count (neutropenia)
• low platelet count (thrombocytopenia)
• skin, lip, eye, or genital ulcers (Stevens-Johnson syndrome and Lyell's syndrome)
• breathing difficulties due to bronchospasm
• ringing in the ears (tinnitus)
• hypersensitivity of the skin
• 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 gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "Important information before taking Skudexa")
• speech disorders
• extreme pupil dilation
• low blood sugar
• hiccups.

The patient should inform their doctor if they experience any side effects, including any not listed in this leaflet. The patient should also inform their doctor if they experience any side effects related to the stomach or intestines (e.g., stomach pain, heartburn, or bleeding) if they have had similar side effects in the past due to long-term use of anti-inflammatory medicines, especially in elderly patients. The most common side effects during treatment with Skudexa are nausea and dizziness, which occur in more than 1 in 10 patients. When taking non-steroidal anti-inflammatory medicines, fluid retention and swelling (especially of the ankles and feet) may occur, as well as increased blood pressure and heart failure. Taking such medicines as Skudexa may be associated with a small increased 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 medicines may rarely cause fever, headache, and stiffness of the neck/cervical spine.

Reporting side effects

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

5. How to store Skudexa

Keep out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and blister after "EXP". The expiry date refers to the last day of that month. This medicine does not require any special storage conditions. The blisters should be kept in the outer packaging to protect from light. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Skudexa contains

• The active substances of Skudexa are tramadol hydrochloride and dexketoprofen. Each tablet contains 75 mg tramadol hydrochloride and 25 mg dexketoprofen.
• Other ingredients are: Tablet core: microcrystalline cellulose, maize starch, sodium carboxymethylcellulose, sodium stearyl fumarate, colloidal anhydrous silica. Tablet coating: Opadry II white 85F18422, consisting of polyvinyl alcohol, titanium dioxide (E 171), macrogol/PEG 3350, talc.

What Skudexa looks like and contents of the pack

Skudexa tablets are almost white to slightly yellowish, elongated, coated tablets with a score line on one side and "M" embossed on the other side. The pack contains 4, 10, 15, 20, 30, 50, or 100 coated tablets, and a multipack containing 5 packs of 100 coated tablets. Not all pack sizes may be marketed.

Marketing authorization holder

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

Manufacturer

Menarini – Von Heyden GmbH, Leipziger Strasse 7-13, 01097 Dresden, Germany This medicinal product is authorized in the Member States of the European Economic Area under the following names: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, United Kingdom (Northern Ireland): Skudexa France: Skudexum Spain: Enanplus Italy: Lenizak Date of last revision of the leaflet: 12/2022