Package Insert: Information for the User

Enanplus 75 mg/25 mg Film-Coated Tablets

tramadol hydrochloride/dexketoprofen

Read this package insert carefully before you start taking this medicine, because it contains important information for you.

• Keep this package insert, as you may need to read it again.

If you have any questions, consult your doctor or pharmacist.

• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, even if they are not listed in this package insert. See section 4.

6. Contents of the pack and additional information

Enanplus contains the active ingredients hydrochloride of tramadol and dexketoprofen.

Tramadol hydrochloride is a pain reliever belonging to the opioid group that acts on the central nervous system. It relieves pain by acting on specific nerve cells in the brain and spinal cord.

Dexketoprofen is a pain reliever belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs).

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

You should consult a doctor if you do not feel better or if you get worse.

Do not take Enanplus

-if you are allergic to dexketoprofen, tramadol hydrochloride, or any of the other components of this medication (listed in section 6)

-if you are allergic to acetylsalicylic acid or another nonsteroidal anti-inflammatory drug (NSAID)

-if you have had asthma attacks, acute allergic rhinitis (a short period of nasal mucosa inflammation), nasal polyps (fleshy formations in the nasal cavity due to allergy), urticaria (skin eruption), angioedema (face, eye, lip, or tongue swelling, or difficulty breathing) or chest wheezing after taking acetylsalicylic acid or other NSAIDs

-if you have had photoallergic or phototoxic reactions (a special form of skin redness or burns exposed to sunlight) during the use of ketoprofen (an NSAID) or fibrates (medications used to reduce blood lipid levels)

• if you have peptic ulcers, stomach or intestinal bleeding, or if you have had stomach or intestinal bleeding in the past, including if it was due to previous use of NSAIDs
• if you have chronic digestive problems (e.g., indigestion, stomach burning)

-if you have chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis)

-if you have severe heart failure, moderate to severe renal insufficiency, or severe liver insufficiency

-if you have bleeding disorders or blood coagulation disorders

-if you are severely dehydrated (have lost a lot of body fluid) due to vomiting, diarrhea, or inadequate fluid intake

-if you have acute alcohol intoxication, sleeping pills, analgesics, or medications that affect mood and emotions

-if you are also taking monoamine oxidase inhibitors (MAOIs) (certain medications used to treat depression) or if you have taken them in the last 14 days before starting treatment with this medication (see "Use of Enanplus with other medications")

-if you have epilepsy or experience seizures, as the risk of these seizures may increase

-if you have difficulty breathing

-if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor before starting to take Enanplus:

-if you are allergic or have had allergic problems in the past;

-if you have kidney, liver, or heart diseases (hypertension and/or heart failure), as well as fluid retention or have had these diseases in the past;

-if you are taking diuretics;

-if you have heart problems, a history of strokes, or think you may be at risk for these conditions (e.g., if you have high blood pressure, diabetes, high cholesterol, or are a smoker) you must consult this treatment with your doctor. Medications like this can be associated with a small increase in the risk of heart attacks or strokes. Any risk is more likely to occur when high doses and prolonged treatments are used. Do not exceed the recommended dose or treatment duration;

-if you are an elderly patient: you may be more likely to experience adverse effects (see section 4). If these occur, consult your doctor immediately;

-if you are a woman with fertility problems: This medication may affect your fertility, so do not take it if you are planning to become pregnant or are undergoing fertility studies;

-if you have blood and blood cell production disorders;

-if you have systemic lupus erythematosus or mixed connective tissue disease (autoimmune diseases that affect connective tissue);

-if you have had chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the past;

-if you have chronic stomach or intestinal problems;

-if you have an infection; see the "Infections" heading below;

-if you are taking other medications that increase the risk of peptic ulcers or bleeding, such as corticosteroids, certain antidepressants (SSRIs), aspirin, or anticoagulants like warfarin. In these cases, consult your doctor before taking this medication: your doctor may prescribe an additional medication to protect your stomach;

-if you have depression and are taking antidepressants, as some may interact with tramadol (see "Other medications and Enanplus");

-if you are taking other medications that contain the same active ingredients as this medication, do not exceed the maximum daily dose of dexketoprofen or tramadol;

-if you think you have opioid addiction;

-if you have altered consciousness (feel like you are going to faint);

-if you are in shock (a sign of this state may be cold sweat);

-if you have increased intracranial pressure (possibly after a head injury or brain disease);

-if you have difficulty breathing;

-if you have porphyria.

Tramadol can cause physical and psychological dependence. When tramadol is taken for a prolonged period, its effect may decrease, requiring higher doses (development of tolerance). In patients with a tendency to abuse medications or those with medication dependence, Enanplus treatment should only be carried out for short periods of time and under strict medical supervision.

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

Talk to your doctor if you experience any of the following symptoms while taking Enanplus: extreme fatigue, loss of appetite, severe abdominal pain, nausea, vomiting, or low blood pressure. This may indicate that you have adrenal insufficiency (low cortisol levels). If you experience any of these symptoms, inform your doctor, and they will decide if you should take a hormone supplement.

Tramadol is metabolized in the liver by an enzyme. Some people have a variation of this enzyme, and this can affect each person differently. In some people, it may be difficult to achieve sufficient pain relief, while others may be more likely to experience severe adverse effects. If you notice any of the following adverse effects, stop taking this medication and consult a doctor immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, general discomfort, or vomiting, constipation, loss of appetite.

There is a weak risk that you may experience a serotonin syndrome that can occur after taking tramadol in combination with certain antidepressants or tramadol alone. Consult your doctor immediately if you experience any of the symptoms associated with this severe syndrome (see section 4 "Possible adverse effects").

Respiratory disorders related to sleep

Enanplus may cause respiratory disorders related to sleep, such as central sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). These symptoms may include pauses in breathing during sleep, nocturnal awakenings due to difficulty breathing, difficulty maintaining sleep, or excessive daytime somnolence. If you or someone else observes these symptoms, consult your doctor. Your doctor may consider reducing the dose.

Infections

Enanplus may mask the signs of an infection, such as pain. Therefore, Enanplus may delay the appropriate treatment of the infection, which may increase the risk of complications. This has been observed in pneumonia caused by bacteria and skin infections related to varicella. If you take this medication while having an infection and the infection symptoms persist or worsen, consult a doctor without delay.

During varicella, it is recommended to avoid using this medication.

Children and adolescents

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

Use in children with respiratory problems

Tramadol should not be used in children with respiratory problems, as the symptoms of tramadol toxicity may worsen in these children.

Use of Enanplus with other medications

Inform your doctor if you are using, have used recently, or may need to use any other medication, including those obtained without a prescription. There are some medications that should not be taken together, and others that may require a dose adjustment if taken together.

Always inform your doctor if, in addition to Enanplus, you are taking any of the following medications:

Associations with Enanplus not recommended:

-Acetylsalicylic acid, corticosteroids, or other anti-inflammatory medications

-Warfarin, heparin, or other medications used to prevent blood clotting

-Lithium, used to treat certain mood disorders

-Metotrexate, used to treat rheumatoid arthritis and cancer

-Hidantoins and phenytoin, used to treat epilepsy

-Sulfamethoxazole, used to treat bacterial infections

-Monamine oxidase inhibitors (MAOIs) (medications for depression).

Associations with Enanplus that require caution:

-Inhibitors of the enzyme cyclooxygenase (COX), diuretics, beta-blockers, and angiotensin II antagonists, used to control high blood pressure and heart conditions

-Pentoxifylline, used to treat chronic venous ulcers

-Zidovudine, used to treat viral infections

-Chlorpropamide and glibenclamide, used to treat diabetes

-Aminoglycoside antibiotics, used to treat bacterial infections.

-The concomitant use of Enanplus and sedatives such as benzodiazepines or related medications increases the risk of somnolence, respiratory depression, coma, and may be potentially fatal. Therefore, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes Enanplus together with sedatives, the dose and duration of concomitant treatment should be limited. Inform your doctor about all sedatives you are taking and follow your doctor's recommended dose carefully. It may be helpful to inform friends or family members to be aware of the signs and symptoms mentioned above. Contact your doctor when you experience these symptoms.

Associations with Enanplus to be aware of:

-Quinolones (e.g., ciprofloxacin, levofloxacin), used to treat bacterial infections

-Ciclosporin or tacrolimus, used to treat autoimmune diseases and organ transplants

-Streptokinase and other thrombolytic and fibrinolytic medications; that is, medications used to dissolve blood clots

-Probenecid, used to treat gout

-Digoxin, used to treat chronic heart failure

-Mifepristone, used to terminate pregnancy

-SSRIs (selective serotonin reuptake inhibitors)

-Antiplatelet agents used to reduce platelet aggregation and blood clot formation

• Tenofovir, deferasirox, pemetrexed.

The analgesic effect of tramadol may be reduced and the duration of action shortened if you are also taking medications that contain:

• Carbamazepine (for epilepsy)
• Buprenorphine, nalbuphine, or pentazocine (analgesics)
• Ondansetron (prevents nausea)

The risk of adverse effects increases:

• if you take tranquilizers, sleeping pills, other analgesics like morphine and codeine (also used to treat cough), or alcohol while taking Enanplus. You may feel drowsy or feel like you are going to faint. Consult your doctor if this occurs.
• if you are taking medications that may cause seizures (e.g., certain antidepressants or antipsychotics). The risk of having a seizure may increase if you take Enanplus at the same time. Your doctor will inform you if Enanplus is suitable for you.
• if you are taking certain antidepressants. Enanplus may interact with these medications and may cause a serotonin syndrome (see section 4 "Possible adverse effects").
• • if you take anticoagulants (medications to thin the blood), e.g., warfarin, together with this medication. The effect of these medications may affect blood coagulation and may cause bleeding.

Enanplus and alcohol

Do not take alcohol during Enanplus treatment, as it may increase the effect of the medication.

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

Pregnancy, breastfeeding, and fertility

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

Dexketoprofen may cause kidney and heart problems in your fetus. It may affect your predisposition and that of your baby to bleed and may delay or prolong labor more than expected. From week 20 of pregnancy, dexketoprofen may cause kidney problems in your fetus, which may cause low amniotic fluid levels (oligohydramnios) or constriction of a blood vessel (ductus arteriosus) in the baby's heart.

Tramadol is excreted in breast milk.

The use of Enanplus is contraindicated during pregnancy as well as during breastfeeding.

Driving and operating machinery

Enanplus may affect your ability to drive and operate machinery, as it may cause dizziness, blurred vision, or somnolence as adverse effects of treatment. This occurs mainly when Enanplus is taken with medications that affect mood and emotions or when taken with alcohol.

If you are affected, do not drive or operate machinery until the symptoms disappear.

This medication contains less than 1 mmol of sodium (23 mg) per dose unit; it is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

The effective dose should be the lowest dose necessary to alleviate symptoms. If you have an infection, consult a doctor immediately if symptoms (pain) persist or worsen (see section 2).

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

The recommended dose is, in general, one coated tablet (corresponding to 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen) every 8 hours, without exceeding three coated tablets per day (corresponding to 225 mg of tramadol hydrochloride and 75 mg of dexketoprofen) and without exceeding 5 days of treatment.

Use in children and adolescents

Enanplus is not suitable for children and adolescents.

Older patients

If you are 75 years or older, your doctor may recommend prolonging the dosing interval, as your body may eliminate the medication more slowly.

Patients with severe liver or kidney disease/dialysis:

Patients with severe liver or kidney disease should not take Enanplus.

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

In case of liver dysfunction, if your case is mild or moderate, your doctor may recommend prolonging the dosing interval.

Swallow the tablet with a sufficient amount of liquid (preferably with a glass of water).

Food delays the absorption of Enanplus, take the tablet at least 30 minutes before meals for faster action.

The groove serves to help break the tablet if you have difficulty swallowing it whole.

If you take more Enanplus than you should

If you have taken too much medication, immediately inform your doctor or go to the emergency service of your nearest hospital or call the Toxicological Information Service, phone: 91.562.04.20, indicating the medication and the amount taken. Please remember to always carry the medication packaging or this leaflet with you.

The symptoms of overdose of this medication are:

• Vomiting, loss of appetite, stomach pain, drowsiness, dizziness/dizziness, disorientation, headache (due to dexketoprofen).
• Pupil constriction, vomiting, heart failure, loss of consciousness, seizures, and difficulty breathing (due to tramadol).

If you forget to take Enanplus

Do not take a double dose to compensate for the missed doses. Take the next dose when due (in accordance with section 3 "How to take Enanplus").

If you interrupt treatment with Enanplus

Generally, no post-treatment effects are expected after stopping Enanplus treatment.

However, in rare cases, patients who have been taking Enanplus tablets for some time may feel unwell if they stop taking it suddenly. They may feel agitation, anxiety, nervousness, or tremors, confusion, hyperactivity, difficulty sleeping, and gastrointestinal or stomach disorders. Rarely, people may experience panic attacks, hallucinations, delirium, paranoia, or feel a loss of identity. They may experience unusual perceptions such as itching, tingling, and numbness, tinnitus. Very rarely, other unusual symptoms have been observed such as confusion, delirium, feeling detached from oneself (derealization), change in perception of reality (despersonalization), illusions of persecution (paranoia). Please consult your doctor if you experience any of these effects after stopping Enanplus.

If you have any other doubts about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The possible side effects are listed below, grouped by how likely they are to occur.

Seek medical attention immediately if you experience symptoms of an allergic reaction such as swelling of the face, tongue, and/or throat, and/or difficulty swallowing or breathing, along with difficulty breathing.

Stop using Enanplus if you experience skin rash, any injury inside the mouth or on mucous membranes, or any sign of allergy.

Very common side effects (may affect more than 1 in 10 people):

• Nausea/dyspepsia
• Dizziness

Common side effects (may affect up to 1 in 10 people):

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

Uncommon side effects (may affect up to 1 in 100 people):

• Increased platelet count
• Effects on the heart and blood circulation (strong heartbeats, rapid heartbeats, feeling of fainting or collapse), low blood pressure. These side effects may occur especially when patients are in an upright position or under physical stress.
• High or very high blood pressure
• Swelling of the larynx (laryngeal edema)
• Low potassium levels in the blood
• Psychotic changes
• Swelling around the eyes
• Shallow or slow breathing
• Feeling of discomfort
• Blood in urine
• Sensation of spinning
• Insomnia or difficulty sleeping
• Nervousness/anxiety
• Hot flushes
• Flatulence
• Fatigue
• Pain
• Sensation of fever or chills, general feeling of discomfort
• Altered blood test results
• Sensation of nausea (having hiccups)
• Sensation of pressure or swelling in the stomach
• Swelling of the stomach
• Reactions on the skin (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
• Peptic ulcer, perforation of peptic ulcer, or bleeding, which may manifest with vomiting blood or black stools
• Prostate problems
• Swelling of the liver (hepatitis), liver damage
• Acute kidney failure
• Slow heart rate
• Seizures
• Allergic/anaphylactic reactions (e.g., difficulty breathing, wheezing, skin inflammation) and shock (sudden circulatory failure)
• Transient loss of consciousness (syncope)
• Hallucinations
• Fluid retention and swelling of the ankles.
• Loss or changes in appetite
• Acne
• Lower back pain
• Frequent or infrequent urination, with difficulty or pain.
• M menstrual problems
• Abnormal sensations (e.g., itching, tingling, loss of sensation)
• Tremors, muscle spasms, uncoordinated movements, muscle weakness
• Confusion
• Sleep disorders and nightmares
• Perceptual changes
• Blurred vision, pupil constriction
• Lack of air

Rare side effects (may affect up to 1 in 10,000 people):

• Pancreatitis
• Renal problems
• Reduced blood cell count (neutropenia)
• Reduced platelet count in the blood (thrombocytopenia)
• Ulcers on the skin, mouth, eyes, and genital areas (Stevens-Johnson syndrome and Lyell syndrome)
• Difficulty breathing due to narrowing of the airways
• Tinnitus (ringing in the ears)
• Sensitive skin
• Photophobia (sensitivity to light)

Unknown (frequency not estimable from available data):

• Serotonin syndrome, which may manifest with changes in mental state (e.g., agitation, hallucinations, coma), and other effects, such as fever, increased heart rate, unstable blood pressure, involuntary muscle contractions, muscle rigidity, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) (see section 2 "what you need to know before taking Enanplus").
• Speech changes
• Extreme pupil dilation
• Low blood sugar levels
• Hiccup

Inform your doctor immediately if you notice any gastrointestinal side effects at the beginning of treatment (e.g., stomach pain or burning, bleeding), if you have previously experienced any of these side effects due to prolonged treatment with anti-inflammatory drugs, and especially if you are an elderly patient.

The most common side effects during treatment with Enanplus are nausea and dizziness, which affect more than 1 in 10 patients.

During treatment with NSAIDs, cases of fluid retention and swelling (especially in ankles and legs), increased blood pressure, and heart failure have been reported.

Medicines like Enanplus may be associated with a small increased risk of suffering a heart attack or stroke.

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

Reporting of side effects

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

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the carton after CAD. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature.

Store in the original packaging to protect it from light.

Medications should not be thrown down the drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Enanplus:

• The active principles are tramadol hydrochloride and dexketoprofen. Each tablet contains: 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen.
• The other components are:

Tablet core: Microcrystalline cellulose;Pre-gelatinized cornstarch;Sodium croscarmellose; Sodium stearate fumarate; Anhydrous colloidal silica.

Coating:Opadry II white 85F18422 composed of polyvinyl alcohol; Titanium dioxide; Macrogol/PEG 3350; Talc.

Appearance of the product and contents of the packaging:

Coated tablets that are almost white or slightly yellowish, oval-shaped, with a notch on one face and an “M” inscribed on the other face, in plastic/aluminum blisters for manual pressure extraction.

Enanplus is presented in packaging of2, 4, 10, 15, 20, 30, 50 or 100 coated tablets with a film coatingand in multi-packaging composed of 5 packaging units, each containing 100 coated tablets with a film coating.

Only some sizes of packaging may be commercially available.

Holder of the marketing authorization and responsible for manufacturing:

Holder of the marketing authorization

LABORATORIOS MENARINI, S.A.

Alfons XII, 587 - Badalona (Barcelona)

Spain

Responsible for manufacturing

Menarini – Von Heyden GmbH

Leipziger Strasse 7-13

01097 Dresden

Germany

This medicine is authorized in the member states of the European Economic Area with the following names:

Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Finland, Greece, Hungary, Ireland, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovak Republic, Slovenia, Sweden, United Kingdom (Northern Ireland): Skudexa

France: Skudexum

Italy: Lenizak

Spain: Enanplus

Last review date of this leaflet: December 2022

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/