Skudexa 75 mg/25 mg film-coated tablets

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor.
• 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. This includes any possible side effects not listed in this leaflet. See section 4.

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

• if you are allergic to dexketoprofen, to tramadol hydrochloride or any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to acetylsalicylic acid (aspirin) or to other NSAIDs
• if you have suffered attacks of asthma, acute allergic rhinitis (a short period of inflamed lining of the nose), nasal polyps (lumps in the nose due to allergy), urticaria (skin rash), angioedema (swollen face, eyes, lips, or tongue, or respiratory distress) or wheezing in the chest after taking acetylsalicylic acid or other non-steroidal anti-inflammatory medicines
• if you have had photoallergic or phototoxic reactions (reddening and/or blistering of the skin exposed to sunlight) while taking ketoprofen (a NSAID) or fibrates (drugs used to lower the level of fats in the blood)
• if you have a peptic ulcer, stomach or bowel bleeding or if you have suffered in the past from stomach or bowel bleeding, ulceration or perforation, including that due to previous use of NSAIDs
• if you have chronic digestive problems (e.g. indigestion, heartburn)
• if you have bowel disease with chronic inflammation (Crohn’s disease or ulcerative colitis)
• if you have serious heart failure, moderate or serious kidney problems or serious liver problems
• if you have a bleeding disorder or a blood clotting disorder
• if you are severely dehydrated (have lost a lot of body fluids) due to vomiting, diarrhoea or insufficient intake of fluids
• if you have acute poisoning with alcohol, sleeping pills, pain relievers, or medicines that affect mood and emotions
• if you are also taking monoamine oxidase inhibitors (MAOIs) (certain medicines used for the treatment of depression) or have taken them in the last 14 days before treatment with this medicine (see “Other medicines and Skudexa”)
• if you have epilepsy of suffer from fits, because the risk of a fit may increase
• if you are breathing with difficulty
• if you are pregnant or breast feeding.

Talk to your doctor before taking Skudexa:

• if you have an allergy, or if you 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 have suffered from any of these problems in the past
• if you are taking diuretics
• if you have heart problems, previous stroke or think that you might be at risk of these conditions (for example if you have high blood pressure, diabetes or high cholesterol or are a smoker) you should discuss your treatment with your doctor; medicines such as this medicine may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. Any risk is more likely with high doses and prolonged treatment. Do not exceed the recommended dose or duration of treatment
• if you are elderly: you may be more likely to suffer from side effects (see section 4). If any of these occur, consult your doctor immediately
• if you are a woman with fertility problems: this medicine may affect your fertility, therefore you should not take it if you are planning to become pregnant or you are having fertility tests
• have a disorder in the formation of blood and blood cells
• if you have systemic lupus erythematosus or mixed connective tissue disease (immune system disorders that affect connective tissue)
• if you have suffered in the past from a chronic inflammatory disease of the bowel (ulcerative colitis, Crohn’s disease)
• if you have or have suffered in the past from other stomach or bowel problems
• if you have an infection - please see heading “Infections” below
• if you are taking other medicines that increase the risk of peptic ulcer or bleeding, e.g. oral steroids, some antidepressants (those of the SSRI type, i.e. Selective Serotonin Reuptake Inhibitors), drugs that prevent blood clots such as acetylsalicylic acid or anticoagulants such as warfarin. In such cases, consult your doctor before taking this medicine: he/she may want you to take an additional medicine to protect your stomach
• if you suffer from depression and you are taking antidepressant as some of them may interact with tramadol (see “Other medicines and Tramadol”)
• if you are taking other medicines containing the same active substances in this medicine, do not exceed the maximum daily doses of dexketoprofen or tramadol
• if you think that you are addicted to other pain relievers (opioids)
• if you have consciousness disorders (if you feel that you are going to faint)
• if you are in a state of shock (cold sweat may be a sign of this)
• if you have increased pressure in the brain (possibly after a head injury or brain disease)
• if you have difficulty in breathing
• if you have porphyria.

Tramadol may lead to physical and psychological addiction. When this medicine is taken for a long time, its effect may decrease, so that higher doses have to be taken (tolerance development). In patients with a tendency to abuse medicines or who are dependent on medicines, treatment with Skudexa should only be carried out for short periods and under strict medical supervision.

Tell your doctor if any of these problems occurs during Skudexa treatment or if they applied in the past.

Talk to your doctor if you experience any of the following symptoms while taking Skudexa: extreme fatigue, lack of appetite, severe abdominal pain, nausea, vomiting or low blood pressure. This may indicate that you have adrenal insufficiency (low cortisol levels). If you have these symptoms, contact your doctor, who will decide if you need to take hormone supplement.

Tramadol is transformed in the liver by an enzyme. Some people have a variation of this enzyme and this can affect people in different ways. In some people, they may not get enough pain relief but other people are more likely to get serious side effects. If you notice any of the following side effects, you must stop taking this medicine and seek immediate medical advice: slow or shallow breathing, confusion, sleepiness, small pupils, feeling or being sick, constipation, lack of appetite.

There is a small risk that you may experience a so-called serotonin syndrome that can occur after having taken tramadol in combination with certain antidepressants or tramadol alone. Seek medical advice immediately if you have any of the symptoms related to this serious syndrome (see section 4 “Possible side effects”).

Skudexa can cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep related hypoxemia (low oxygen level in the blood). The symptoms can include breathing pauses during sleep, night awakening due to shortness of breath, difficulties to maintain sleep or excessive drowsiness during the day. If you or another person observe these symptoms, contact your doctor. A dose reduction may be considered by your doctor.

Skudexa may hide signs of infections such as fever and pain. It is therefore possible Skudexa may delay appropriate treatment of infection, which may lead to an increased risk of complications. This has been observed in pneumonia caused by bacteria and bacterial skin infections related to chickenpox. If you take this medicine while you have an infection and your symptoms of the infection persist or worsen, consult a doctor without delay.

During chicken pox it is advisable to avoid use of this medicine.

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

Use in children with breathing problems

Tramadol is not recommended in children with breathing problems, since the symptoms of tramadol toxicity may be worse in these children.

Tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. Some medicines should not be taken together and others may need their doses to be altered when taken together.

Always inform your doctor if you are using or receiving any of the following medicines in addition to Skudexa:

Use with Skudexa is not recommended:

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

Use with Skudexa requires precautions:

• ACE inhibitors, diuretics, beta-blockers and angiotensin II antagonists, used for high blood pressure and heart problems
• Pentoxifylline, used to treat chronic venous ulcers
• Zidovudine, used to treat viral infections
• Chlorpropamide and glibenclamide used for diabetes
• Aminoglycoside antibiotics, used to treat bacterial infections.
• Concomitant use of Skudexa and sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible. However if your doctor does prescribe Skudexa together with sedative medicines the dose and duration of concomitant treatment should be limited by your doctor. Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.

Use with Skudexa requires care:

• Quinolone antibiotics (e.g. ciprofloxacin, levofloxacin) used for bacterial infections
• Ciclosporin or tacrolimus, used to treat immune system diseases and in organ transplant
• Streptokinase and other thrombolytic or fibrinolytic medicines, i.e. medicines used to break up blood clots
• Probenecid, used in gout
• Digoxin, used to treat chronic heart failure
• Mifepristone, used to terminate a pregnancy
• Antidepressants of the selective serotonin reuptake inhibitors type (SSRIs)
• Anti-platelet agents used to reduce platelet aggregation and the formation of blood clots
• Tenofovir, deferasirox, pemetrexed.

The pain-relieving effect of tramadol may be reduced, and the length of time it acts may be shortened, if you also take medicines containing:

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

The risk of side effects increases

• if you take tranquillizers, sleeping pills, other pain relievers such as morphine and codeine (also as cough medicine), or alcohol while you are taking Skudexa. You might feel drowsier or feel that you might faint. If this happens tell your doctor
• if you are taking medicines which may cause convulsions (fits), such as certain antidepressants or antipsychotics. The risk of having a fit may increase if you take Skudexa at the same time. Your doctor will tell you whether Skudexa is suitable for you
• if you are taking certain antidepressants. Skudexa may interact with these medicines and you may experience serotonin syndrome (see section 4 “Possible side effects”)
• if you take anticoagulants (medicines for blood thinning), e.g. warfarin, together with this medicine. The effect of these medicines on blood clotting may be affected and bleeding may occur.

Do not drink alcohol during treatment with Skudexa as it may increase the effect of the medication. For the instruction how to take Skudexa see section 3.

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

Dexketoprofen can cause kidney and heart problems in your unborn baby. It may affect your and your baby’s tendency to bleed and cause labour to be later or longer than expected. From 20 weeks of pregnancy, dexketoprofen can cause kidney problems in your unborn baby, that may lead to low levels of amniotic fluid that surrounds the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the heart of the baby.

Tramadol is excreted into breast milk.

The use of Skudexa is contraindicated in pregnancy as well as during breast-feeding.

Skudexa may affect your ability to drive and handle machines, due to the possibility of dizziness, blurred vision or drowsiness as side effects of treatment. This applies particularly when Skudexa is taken with medicines that affect mood and emotions, or alcohol.

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

This medicinal product contains less than 1 mmol sodium (23mg) per dosage unit, that is to say essentially “sodium-free”.

Skudexa is not suitable for children and adolescents.

If you are aged 75 years or over, your doctor may recommend prolonging the dosage interval because your body may handle the drug more slowly.

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

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

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

Swallow the tablet with a sufficient amount of fluid (preferably with a glass of water). Food delays the absorption of Skudexa, so for a faster effect take the tablet at least 30 minutes before meals. The score line is to help you break the tablet if you have difficulty swallowing it whole.

If you use too much of this medicine, tell your doctor immediately or go to the emergency department of your nearest hospital. Please remember to take this medicine pack or this leaflet with you.

The symptoms of an overdose of this medicine are:

• vomiting, loss of appetite, stomach pain, drowsiness, dizziness/spinning sensation, disorientation, headache (for dexketoprofen)
• contraction of the pupil, vomiting, heart failure, loss of consciousness, convulsions and difficulty in breathing (for tramadol).

Do not take a double dose to make up for a forgotten tablet. Take the next regular dose when it is due (see section 3 “How to take Skudexa”).

Generally there will be no after-effects when treatment with Skudexa is stopped.

However, on rare occasions, patients who have been taking Skudexa tablets for some time may feel unwell if they stop taking them abruptly. They may feel agitated, anxious, nervous or shaky, be confused, hyperactive, have difficulty sleeping and have stomach or bowel disorders. Rarely, people may get panic attacks, hallucinations, delusions, paranoia or feel a loss of identity. They may experience unusual perceptions such as itching, tingling and numbness, and ringing in the ears (tinnitus). Further unusual symptoms, i.e. confusion, delusions, feeling as though you are detached from yourself (depersonalization), and change in perception of reality (derealisation) and delusion of persecution (paranoia) have been seen very rarely. If you experience any of these complaints after stopping Skudexa, please consult your doctor.

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substances are tramadol hydrochloride and dexketoprofen. Each tablet contains: 75 mg of tramadol hydrochloride and 25 mg dexketoprofen.
• The other ingredients are the following:
  Tablet core: microcrystalline cellulose, pregelatinised maize starch, croscarmellose sodium, sodium stearyl fumarate, anhydrous silica colloidal.
  Film-coating: Opadry II white 85F18422 composed of polyvinyl alcohol, titanium dioxide, Macrogol/PEG 3350, talc.

Almost white to slightly yellow, oblong, film-coated tablets with a break-mark on one side and debossed “M” on the other side in plastic/aluminium push-through pill packs.

Skudexa is supplied in packs containing 2, 4, 10, 15, 20, 30, 50 or 100 film-coated tablets and in multipacks comprising 5 cartons, each containing 100 film-coated tablets.

Not all pack sizes may be marketed.

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