Skudexa

Package leaflet: Information for the patient

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Skudexa (Enanplus)
75 mg + 25 mg, film-coated tablets
Tramadoli hydrochloridum + Dexketoprofenum
Skudexa and Enanplus are different trade names for the same medicinal product.
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are similar.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

1. What Skudexa is and what it is 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 Skudexa is and what it is used for

Skudexa contains tramadol hydrochloride and dexketoprofen as active substances.
Tramadol hydrochloride is an analgesic belonging to a 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 an analgesic belonging to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs).
Skudexa is indicated for the short-term symptomatic treatment of moderate to severe acute pain in adults.
Inform your doctor if the patient does not feel better or feels worse after taking the medicine.

2. Important information before using Skudexa

When not to use 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 previously experienced asthma attacks, acute allergic rhinitis (short-term inflammation of the nasal mucosa), nasal polyps (growths inside the nose caused by allergy), urticaria (skin rash), angioedema (swelling of the face, eyes, lips, tongue or associated respiratory symptoms), or wheezing after taking acetylsalicylic acid or another NSAID
• if the patient has previously experienced photosensitivity reactions: photoallergic or phototoxic reactions (particularly as redness and/or blisters on skin exposed to sunlight) while taking ketoprofen (an NSAID) or fibrates (medicines used to lower blood lipid levels)
• if the patient has active gastric and/or duodenal ulcer, or gastrointestinal bleeding, or has previously experienced gastrointestinal bleeding, ulceration or perforation, including cases due to prior use of NSAIDs
• if the patient has chronic digestive problems (e.g. indigestion, heartburn)
• if the patient has inflammatory bowel diseases (Crohn's disease or ulcerative colitis)
• if the patient has severe heart failure, moderate or severe renal or severe hepatic impairment
• if the patient has a tendency to bleed excessively or has coagulation disorders
• if the patient is severely dehydrated (excessive loss of body fluids) due to vomiting, diarrhoea, or inadequate fluid intake
• in cases of acute alcohol intoxication, sedatives, painkillers, or medicines affecting mood and emotions
• if the patient is currently taking monoamine oxidase inhibitors (MAOIs) (some 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 seizures, as seizure risk may increase
• if the patient has difficulty breathing
• if the patient is pregnant or breastfeeding.

Warnings and precautions
Before starting treatment with Skudexa, discuss with your doctor:

• if the patient has allergies or has previously experienced allergic problems

• if the patient has impaired kidney, liver or heart function (hypertension and/or heart failure), fluid retention, or if any of these conditions occurred previously

• in patients taking diuretics

• if the patient has heart problems, history of stroke, or suspected risk factors for these conditions (e.g. high blood pressure, diabetes, high cholesterol, or smoking). In such cases, consult your doctor before using Skudexa. Use of medicines such 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. Do not exceed the recommended dose or duration of treatment

• if the patient is elderly: increased risk of adverse effects (see section 4). In such cases, contact your doctor immediately

• in women with fertility problems: this medicine may impair female fertility and is not recommended in women planning pregnancy or undergoing infertility treatment

• if the patient has disorders of blood or blood cell formation

• if the patient has systemic lupus erythematosus or mixed connective tissue disease (immune system disorders affecting connective tissue)

• if the patient has previously had chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease)

• if the patient has or has previously had other stomach or intestinal disorders

• if the patient has an infection – see below under "Infections"

• if the patient is taking other medicines that increase the risk of gastric or duodenal ulcer or bleeding, e.g. oral corticosteroids, certain antidepressants (SSRIs – selective serotonin reuptake inhibitors), anticoagulants such as acetylsalicylic acid or anticoagulants like warfarin. In such cases, consult your doctor before taking the medicine; the doctor may decide to prescribe an additional protective medicine

• if the patient has depression and is taking antidepressants, as some may interact with tramadol (see "Skudexa and other medicines")

• if the patient is taking other medicines containing the same active substances, do not exceed the maximum daily dose of dexketoprofen or tramadol

• if the patient believes they are dependent on other painkillers (opioids)

• if the patient has impaired consciousness (feeling faint)

• if the patient is in shock (cold sweat may be a symptom)

• 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 used for a prolonged period, its effect may diminish, requiring higher doses (development of tolerance). In patients with a tendency to drug abuse or dependence, treatment with Skudexa should be short-term and under strict medical supervision. Inform your 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, inform the doctor: excessive fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. These may indicate adrenal insufficiency (low cortisol levels). If such symptoms occur, contact your doctor, who will decide whether hormone replacement is necessary.
Tramadol is metabolized in the liver by an enzyme. Some individuals have a genetic variation of this enzyme, which may lead to different effects. In some people, pain relief may be insufficient, while in others, severe adverse effects may be more likely. Discontinue use and contact your doctor immediately if the patient experiences any of the following adverse effects: slowed or shallow breathing, confusion, drowsiness, pinpoint pupils, nausea or vomiting, constipation, or loss of appetite.
Taking tramadol in combination with certain antidepressants or tramadol alone carries a small risk of serotonin syndrome. If the patient experiences any symptoms of severe serotonin syndrome, they should seek immediate medical advice (see section 4 "Possible side effects").
Sleep-related breathing disorders
Skudexa may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels). Symptoms may include breathing pauses during sleep, nocturnal awakenings due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If the patient or another person observes these symptoms, contact a doctor. The doctor may recommend reducing the dose.
Infections
Skudexa may mask symptoms of infection such as fever and pain. Therefore, Skudexa may delay appropriate treatment of infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If the patient takes this medicine during an infection and symptoms persist or worsen, consult a doctor immediately.
Avoid using this medicine during chickenpox.
Children and adolescents
The use of this medicine has not been studied in children and adolescents. Safety and efficacy have not been established, and therefore Skudexa should not be used in children and adolescents.
Use in children with breathing disorders
Tramadol is not recommended in children with breathing disorders, as symptoms of tramadol toxicity may be more severe in these patients.
Skudexa and other medicines
Inform your doctor about all medicines currently taken or recently taken, including those available without prescription, and any medicines the patient plans to take.
Some medicines should not be used together with Skudexa, while others may require dose adjustments when used concurrently. Always inform your doctor if taking any of the following medicines together with Skudexa:
Concomitant use not recommended:

• Acetylsalicylic acid, corticosteroids, or other anti-inflammatory medicines
• Warfarin, heparin, or other anticoagulants
• 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 sedatives such as benzodiazepines or other medicines acting similarly to benzodiazepines may increase the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered if no other treatment options are possible. If your doctor prescribes Skudexa to be used together with sedatives, the dose and duration of treatment should be limited by the doctor. Inform your doctor about all sedative medicines you are taking and strictly follow your doctor's instructions. It may be helpful to inform friends and family that the above symptoms may occur. Contact 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 in transplant patients
• Streptokinase and other thrombolytic or fibrinolytic medicines used to dissolve blood clots
• Probenecid used to treat gout
• Digoxin used to treat chronic heart failure
• Mifepristone used as a medicine to terminate pregnancy
• Selective serotonin reuptake inhibitor (SSRI) antidepressants
• Antiplatelet medicines used to reduce platelet aggregation and blood clot formation
• Tenofovir, deferasirox, pemetrexed.

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

• Carbamazepine (for seizures)
• Buprenorphine, nalbuphine, or pentazocine (painkillers)
• Ondansetron (prevents nausea).

The risk of adverse effects increases:

• if the patient takes sedatives, hypnotics, other painkillers such as morphine and codeine (also for cough), or alcohol while using Skudexa. The patient may feel drowsy or faint. If this occurs, inform the doctor
• if the patient takes medicines that may cause seizures (convulsions), such as certain antidepressants or antipsychotics. The risk of seizures may increase with concomitant use of Skudexa. The doctor will decide whether Skudexa is suitable for the patient
• if the patient takes certain antidepressants. Skudexa may interact with these medicines and cause serotonin syndrome (see section 4 "Possible side effects")
• if the patient takes anticoagulants (blood thinners), e.g. warfarin, together with this medicine. The effect of these medicines on blood clotting may be altered, leading to bleeding.

Use of Skudexa with alcohol
Do not drink alcohol while being treated with Skudexa, as it may intensify the medicine's effects.
Instructions for use of Skudexa – see section 3.
Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
Dexketoprofen may cause kidney and heart problems in the unborn child. This medicine may increase the tendency to bleed in both the mother and child and may delay or prolong labour. From the 20th week of pregnancy, dexketoprofen may cause:
kidney problems in the unborn child – this may lead to reduced amniotic fluid volume surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby's heart.
Tramadol is excreted in breast milk.
Use of Skudexa is contraindicated during pregnancy and while breastfeeding.
Driving and operating machinery
Skudexa may affect the ability to drive and operate machinery due to possible side effects such as dizziness, visual disturbances, or drowsiness during treatment. This is particularly relevant when Skudexa is taken with medicines affecting mood and emotions or with alcohol.
If such symptoms occur, do not drive or operate machinery until symptoms resolve.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is considered practically sodium-free.

3. How to use Skudexa

This medicine should always be taken as directed by the physician. If in doubt, consult the doctor.
The lowest effective dose for the shortest duration necessary to relieve symptoms should be used.
If symptoms of infection (such as fever and pain) persist or worsen, consult a 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 patient's pain. The doctor will also specify the number of tablets to be taken daily and the duration of treatment.

The usual recommended daily dose is 1 coated tablet (equivalent to 75 mg tramadol hydrochloride and 25 mg dexketoprofen) every 8 hours. The total daily dose should not exceed 3 coated tablets (equivalent to 225 mg tramadol hydrochloride and 75 mg dexketoprofen), and treatment should not last longer than 5 days.

Use in children and adolescents
Skudexa must 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 (impaired function)/dialysis patients
Patients with severe liver disease and/or kidney failure must not take Skudexa.

In case of impaired kidney function, if the patient has mild kidney impairment, the doctor may recommend extending the interval between doses.

In case of impaired liver function, if the patient has mild or moderate liver impairment, the doctor may recommend extending the interval between doses.

Skudexa tablets should be swallowed with sufficient liquid (preferably a glass of water).

Food delays the absorption of Skudexa; therefore, to achieve a faster effect, the tablet should be taken at least 30 minutes before a meal. The break line visible on the tablet may help to split it in case of difficulty swallowing the tablet whole.

Use of a higher than recommended dose of Skudexa
If a patient takes more than the recommended dose, a doctor should be contacted immediately or the patient should go to the nearest hospital emergency department. Remember to bring the medicine packaging or the patient leaflet.

Symptoms of overdose include:

• vomiting, loss of appetite, abdominal pain, drowsiness, dizziness/vertigo, disorientation, headache (due to dexketoprofen)
• pinpoint pupils, vomiting, cardiac failure, loss of consciousness, seizures, and breathing difficulties (due to tramadol).

Missed 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 prescribed dosing schedule (see section 3 "How to use Skudexa").

Discontinuation of Skudexa
Withdrawal effects after stopping Skudexa are unlikely.
However, in rare cases, patients who have taken Skudexa for some time may feel unwell if treatment is abruptly discontinued. They may experience agitation, anxiety, nervousness, or feel uneasy, confused, hyperactive, have sleep disturbances, or gastrointestinal disturbances. Rarely, patients may experience panic attacks, hallucinations, delusions, paranoia, or depersonalization. Unusual sensations such as itching, tingling, numbness, and ringing in the ears may occur. Very rarely, additional unusual symptoms such as confusion, delusions, feelings of depersonalization, changes in perception of reality (derealization), and persecutory delusions (paranoia) have been observed. If any of these symptoms occur after stopping Skudexa, consult a doctor.

If there are any further doubts regarding the use of this medicine, consult a doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The possible adverse effects are listed below, grouped according to the likelihood of their occurrence.
Contact a doctor immediately if symptoms of an allergic reaction occur, such as swelling of the face, tongue and/or throat, and/or difficulty swallowing, or hives together with breathing difficulties.
Stop taking Skudexa as soon as possible if the patient notices the appearance of a rash or any changes inside the mouth or on mucous membranes, or any symptoms of allergy.

Very common adverse effects (may affect more than 1 in 10 patients):

• nausea
• dizziness

Common adverse effects (may affect up to 1 in 10 patients):

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

Uncommon adverse effects (may affect up to 1 in 100 patients):

• increased platelet count
• effects on the heart and blood circulation (palpitations, rapid heartbeat, feeling faint or collapse), low blood pressure. These adverse effects may occur especially when the patient is in an upright position or during physical exertion.
• high or very high blood pressure
• swelling of vocal cords (laryngeal oedema)
• decreased potassium levels in the blood
• psychotic disorders
• eye-area swelling
• shallow or slow breathing
• discomfort, abnormal sense of well-being
• blood in urine
• sensation of spinning (vertigo)
• insomnia or difficulty falling asleep
• nervousness/anxiety
• hot flushes
• bloating
• fatigue
• pain
• feeling feverish and chills, general malaise
• abnormal blood test results
• tendency to vomit (vomiting reflex)
• feeling of pressure in the stomach, bloating
• gastritis
• skin reactions (e.g. itching, rash)
• facial swelling

Rare adverse effects (may affect up to 1 in 1,000 patients):

• swelling of lips and throat
• peptic ulcer of the stomach and/or duodenum, perforation or bleeding, which may present as 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 swelling) and shock (sudden circulatory failure)
• transient loss of consciousness (fainting)
• hallucinations
• fluid retention or ankle swelling
• loss of appetite, appetite changes
• acne
• back pain
• frequent urination or reduced urine output, with difficulty or pain
• menstrual disorders
• sensory disturbances (e.g. itching, tingling, numbness)
• tremor, muscle spasms, uncoordinated movements, muscle weakness
• confusion
• sleep disturbances and nightmares
• perceptual disturbances
• blurred vision, pupil constriction
• shortness of breath

Psychiatric adverse effects may occur during treatment with Skudexa. Their intensity and character may vary (depending on the patient's personality and duration of treatment) and may include:

• mood changes (mostly elevated mood, sometimes irritability)
• changes in activity (slowing down, but sometimes increased activity)
• feeling less aware
• reduced ability to make decisions, which may lead to reasoning errors

Worsening of asthma has been reported.
Symptoms of withdrawal may occur after abrupt discontinuation of treatment (see "Discontinuation of Skudexa").
Seizures occurred mainly after administration of high doses of tramadol or when tramadol was used simultaneously with other medicines that may provoke seizures.

Very rare adverse effects (may affect up to 1 in 10,000 patients):

• pancreatitis
• kidney problems
• reduced white blood cell count (neutropenia)
• reduced platelet count (thrombocytopenia)
• skin, lip, eye or genital ulceration (Stevens-Johnson syndrome and Lyell's syndrome)
• shortness of breath due to airway narrowing
• ringing in the ears (tinnitus)
• skin hypersensitivity
• light sensitivity

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

• serotonin syndrome, which may present with changes in mental status (e.g. agitation, hallucinations, coma), as well as other symptoms such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination, and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea) (see section 2. Important information before taking Skudexa)
• speech disorders
• extreme pupil dilation
• decreased blood sugar levels
• hiccups

Patients should inform their doctor if they experience any adverse effects affecting the stomach or intestines at the beginning of treatment (e.g. stomach pain, heartburn or bleeding), especially if they have previously experienced similar adverse effects due to long-term use of anti-inflammatory medicines, particularly in elderly patients.

The most common adverse effects during treatment with Skudexa are nausea and dizziness, which occur in more than 1 in 10 patients.

During administration of non-steroidal anti-inflammatory drugs (NSAIDs), fluid retention and oedema (particularly in ankles and legs), increased blood pressure and heart failure may occur.

Taking medicines such as Skudexa may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.

In patients with immunological disorders affecting connective tissue (systemic lupus erythematosus or mixed connective tissue disease), administration of anti-inflammatory medicines may rarely cause fever, headache and neck stiffness.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store the medicine Skudexa

Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
No special temperature storage requirements.
Store in the original packaging to protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Skudexa contains

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

What Skudexa looks like and contents of the pack
Skudexa tablets are almost white to slightly yellowish, elongated coated tablets with a division line on one side and an embossed "M" on the other.
Pack contents: 10, 20, 30, 50 or 100 coated tablets.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Spain, the country of export:
Laboratorios Menarini, S.A.
Alfons XII, 587
Badalona (Barcelona)
Spain
Manufacturer:
Menarini - Von Heyden GmbH
Leipziger Strasse 7-13, 01097 Dresden, Germany
Parallel importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Spain marketing authorisation number: 711033.0
Parallel import authorisation number: 343/25
This medicinal product is authorised for marketing in the European Economic Area countries under the following names: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Finland, Greece, Hungary, Ireland, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, United Kingdom (Northern Ireland): Skudexa
France: Skudexum
Spain: Enanplus
Italy: Lenizak