DIFENADEX 25 mg ORAL SOLUTION

2. What you need to know before taking Difenadex

Do not take Difenadex

• If you are allergic to dexketoprofen or any of the other components of this medicine (listed in section 6).
• If you are allergic to acetylsalicylic acid or another non-steroidal anti-inflammatory medicine.
• If you have asthma or have suffered from asthma attacks, acute allergic rhinitis (a short period of inflammation of the nasal mucosa), nasal polyps (fleshy growths inside the nose due to allergy), urticaria (skin rash), angioedema (swelling of the face, eyes, lips, or tongue, or difficulty breathing) or wheezing in the chest after taking acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs.
• If you have suffered from photoallergic or phototoxic reactions (a special form of redness or sunburn) while taking ketoprofen (a non-steroidal anti-inflammatory drug) or fibrates (medicines used to reduce blood fat levels).
• If you have a peptic ulcer, stomach or intestinal bleeding, or if you have suffered from bleeding, ulceration, or perforation of the stomach or intestine in the past.
• If you have chronic digestive problems (e.g., indigestion, heartburn).
• If you have suffered from stomach or intestinal bleeding or perforation in the past due to the use of non-steroidal anti-inflammatory drugs (NSAIDs) for pain.

• If you have chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis).
• If you have severe heart failure, moderate to severe kidney failure, or severe liver failure.
• 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 insufficient fluid intake.
• If you are in the third trimester of pregnancy or breastfeeding.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Difenadex:

• If you are allergic or have had allergy problems in the past.
• If you have kidney, liver, or heart disease (high blood pressure and/or heart failure), or fluid retention or have suffered from any of these diseases in the past.
• If you are taking diuretics or have insufficient hydration and reduced blood volume due to excessive fluid loss (e.g., due to excessive urination, diarrhea, or vomiting).
• If you have heart problems, a history of strokes, or think you may be at risk of suffering from these disorders (e.g., you have high blood pressure, suffer from diabetes, have high cholesterol, or are a smoker) you should consult your doctor or pharmacist about this treatment. Medicines like Difenadex may be associated with a small increased risk of suffering from heart attacks ("myocardial infarctions") 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 experience a higher incidence of side effects (see section 4). If these occur, consult your doctor immediately.
• If you are a woman with fertility problems (see section 2, "Pregnancy, breastfeeding, and fertility").
• If you have a blood disorder and blood cell production disorder.
• If you have systemic lupus erythematosus or mixed connective tissue disease (diseases of the immune system that affect connective tissue).
• If you have suffered from chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the past.
• If you have suffered from stomach or intestinal disorders in the past.
• If you have an infection; see the "Infections" heading below.
• If you are taking other medicines that increase the risk of peptic ulcers or bleeding, such as oral corticosteroids, some antidepressants (of the SSRI type, Selective Serotonin Reuptake Inhibitors), agents that prevent blood clot formation such as acetylsalicylic acid (aspirin) or anticoagulants like Warfarin. In these cases, consult your doctor before taking this medicine: it may be that your doctor prescribes an additional medicine to protect your stomach (e.g., misoprostol or other medicines that block the production of stomach acid).
• If you have asthma combined with chronic rhinitis or sinusitis, and/or nasal polyps, as you have a higher risk of being allergic to acetylsalicylic acid and/or NSAIDs than the rest of the population. The administration of this medicine may cause asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

Infections

Difenadex may hide the signs of an infection, such as fever and pain. Consequently, this medicine may delay the appropriate treatment of the infection, which may increase the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to chickenpox. If you take this medicine while having an infection and the symptoms of the infection persist or worsen, consult a doctor without delay.

Avoid using this medicine if you have chickenpox.

Children and adolescents

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

Other medicines and Difenadex

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine, including those obtained without a prescription. There are some medicines that should not be taken together, and others may need a dose change if taken together.

Always inform your doctor, dentist, or pharmacist if, in addition to this medicine, you are taking any of the following medicines:

Not recommended combinations:

• Acetylsalicylic acid, corticosteroids, and other anti-inflammatory drugs.
• Warfarin, heparin, and other medicines used to prevent blood clot formation.
• Lithium, used to treat some mood disorders.
• Methotrexate (cancer and immunosuppressive medicine), used at high doses of 15 mg/week.
• Hydantoins and phenytoin, used for epilepsy.
• Sulfamethoxazole, used for bacterial infections.

Combinations that require caution:

• ACE inhibitors, diuretics, and angiotensin II antagonists, used for high blood pressure and heart disorders.
• Pentoxifylline and oxpentifylline, used to treat chronic venous ulcers.
• Zidovudine, used to treat viral infections.
• Aminoglycoside antibiotics, used for bacterial infections.
• Sulfonylureas (e.g., chlorpropamide and glibenclamide) used for diabetes.
• Methotrexate, used at low doses, less than 15 mg/week.

Combinations to be taken into account:

• Quinolones (e.g., ciprofloxacin, levofloxacin) used for bacterial infections.
• Cyclosporine or tacrolimus, used to treat immune system diseases and organ transplants.
• Streptokinase and other thrombolytic and fibrinolytic medicines; i.e., medicines used to dissolve blood clots.
• Probenecid, used for gout.
• Digoxin, used in the treatment of chronic heart failure.
• Mifepristone, used as an abortifacient (for pregnancy termination).
• Antidepressants of the SSRI type (Selective Serotonin Reuptake Inhibitors).
• Antiplatelet agents used to reduce platelet aggregation and blood clot formation.
• Beta-blockers, used for high blood pressure and heart disorders.
• Tenofovir, deferasirox, pemetrexed.

If you have any doubts about taking other medicines with Difenadex, consult your doctor or pharmacist.

Taking Difenadex with food, drinks, and alcohol

Generally, it is recommended to take the medicine with meals to reduce the possibility of causing stomach disorders (see also section 3, "Method of administration").

The use of NSAIDs in combination with alcohol may worsen the adverse reactions caused by the active ingredient.

Pregnancy, breastfeeding, and fertility

Do not take this medicine during the last three months of pregnancy or during breastfeeding. Difenadex may cause kidney and heart problems in your fetus. It may affect your and your baby's tendency to bleed and delay or prolong labor more than expected. You should not take Difenadex during the first six months of pregnancy unless it is clearly necessary and as indicated by your doctor. If you need treatment during this period or while trying to become pregnant, you should take the minimum dose for the shortest possible time. From the 20th week of pregnancy, Difenadex may cause kidney problems in your fetus if taken for more than a few days, which may cause low levels of amniotic fluid surrounding the baby (oligohydramnios) or constriction of a blood vessel (ductus arteriosus) in the baby's heart. If you need treatment for more than a few days, your doctor may recommend additional checks.

The use of this medicine may impair fertility, so it is not recommended to use it while trying to conceive or while investigating a fertility problem.

Driving and using machines

This medicine may slightly affect your ability to drive and use machines, as it may cause dizziness or drowsiness and visual disturbances as side effects of treatment. If you notice these effects, do not use machines or drive until these symptoms disappear. Ask your doctor for advice.

Difenadex contains saccharose, methyl parahydroxybenzoate, ethanol, and sodium

It may cause allergic reactions (possibly delayed) because it contains methyl parahydroxybenzoate.

This medicine contains saccharose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medicine.

This medicine contains 13.8 mg of alcohol (ethanol) in each sachet, which is equivalent to 1.4 mg/ml (0.14% p/v). The amount in 10 ml of this medicine is equivalent to less than 1 ml of beer or wine.

The small amount of alcohol in this medicine does not produce any noticeable effect.

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

3. How to take Difenadex

Follow exactly the administration instructions of this medicine contained in this leaflet or as indicated by your doctor or pharmacist. In case of doubt, ask your doctor or pharmacist.

The necessary dose of the medicine may vary depending on the type, intensity, and duration of the pain.

The lowest effective dose should be used for the shortest necessary time to relieve symptoms. If you have an infection, consult a doctor without delay if the symptoms (such as fever and pain) persist or worsen (see section 2).

Adults over 18 years

Generally, the recommended dose is 1 sachet (25 mg of dexketoprofen) every 8 hours, not exceeding 3 sachets per day (75 mg).

Elderly patients or patients with kidney or liver failure

If you are an elderly patient or suffer from mild kidney problems or mild to moderate liver problems, it is recommended to start treatment with a maximum of 2 sachets per day (50 mg of dexketoprofen).

In elderly patients, this initial dose may be increased later according to the general recommended dose (75 mg of dexketoprofen) if the medicine has been well tolerated.

You should not use dexketoprofen if you have moderate or severe kidney problems or severe liver problems. Consult your doctor or pharmacist if you are unsure.

Use in children and adolescents

This medicine should not be used in children and adolescents (under 18 years).

Method of administration

The oral solution can be taken directly from the sachet or after pouring the contents into a glass of water. Once the sachet is opened, consume the entire contents.

The medicine can be taken with or without food. Taking the medicine with food helps to reduce the risk of stomach disorders; however, if your pain is more intense and you need faster relief, take the sachet on an empty stomach (at least 15 minutes before any meal or food intake) because it will be absorbed more easily (see section 2, "Taking Difenadex with food, drinks, and alcohol").

Duration of treatment

Treatment should not exceed 4 days. If the pain persists after this period, worsens, or other symptoms appear, you should stop treatment and consult your doctor or pharmacist.

If you take more Difenadex than you should

Consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken. It is recommended to take the package and leaflet of the medicine to the healthcare professional.

If you forget to take Difenadex

Do not take a double dose to make up for forgotten doses. Take the next dose when scheduled (according to section 3, "How to take Difenadex").

If you have doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Possible adverse effects are detailed below according to their frequency.

Since the list is based in part on adverse effects observed with the oral use of tablets, and the oral solution in sachets is absorbed more quickly than tablets, it is possible that the actual frequency of adverse effects (gastrointestinal) may be higher in the oral solution in sachets.

Frequent Adverse Effects(may affect up to 1 in 10 people)

Nausea and/or vomiting, mainly pain in the upper abdominal quadrant, diarrhea, digestive disorders (dyspepsia).

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

Rotatory sensation (vertigo), dizziness, drowsiness, sleep disorders, nervousness, headache, palpitations, hot flashes, inflammation of the stomach wall (gastritis), constipation, dry mouth, flatulence, skin rash, fatigue, pain, febrile sensation, and chills, general malaise.

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

Peptic ulcer, perforation of peptic ulcer or bleeding (which may manifest with vomiting of blood or black stools), fainting, high blood pressure, slow breathing, fluid retention, and peripheral edema (e.g., swelling of ankles), laryngeal edema, loss of appetite (anorexia), abnormal sensation, pruritic rash, acne, increased sweating, lower back pain, frequent urination, menstrual disorders, prostate disorders, abnormal liver function tests (blood tests), liver cell damage (hepatitis), acute kidney failure.

Very Rare Adverse Effects (may affect up to 1 in 10,000 people)

Anaphylactic reaction (hypersensitivity reaction that can also lead to collapse), ulcers on the skin, mouth, eyes, and genital areas (Stevens-Johnson syndrome and Lyell syndrome), swelling of the face or swelling of the lips and throat (angioedema), difficulty breathing due to narrowing of the airways (bronchospasm), shortness of breath, tachycardia, low blood pressure, pancreatitis, blurred vision, ringing in the ears (tinnitus), sensitive skin, sensitivity to light, itching, kidney problems. Decrease in the number of white blood cells (neutropenia), decrease in the number of platelets (thrombocytopenia).

Inform your doctor immediately if you notice any adverse effect of a gastrointestinal type at the start of treatment (e.g., stomach pain or burning or bleeding), if you have previously suffered from any of these adverse effects due to prolonged treatment with non-steroidal anti-inflammatory drugs, and especially if you are an elderly patient.

Stop taking this medicine immediately if you notice the appearance of a skin rash or any lesion inside the mouth or on the genitals, or any other sign of allergy.

During treatment with non-steroidal anti-inflammatory drugs, cases of fluid retention and swelling (especially in ankles and legs), increased blood pressure, and heart failure have been reported.

Medicines like Difenadex may be associated with a small increased risk of suffering a heart attack ("myocardial infarction") or stroke ("stroke").

In patients with immune system disorders that affect connective tissue (systemic lupus erythematosus or mixed connective tissue disease), non-steroidal anti-inflammatory drugs can rarely cause fever, headache, and neck stiffness.

The most commonly observed adverse effects are of a gastrointestinal type. Peptic ulcers, perforation, or gastrointestinal bleeding may occur, sometimes fatal, especially in elderly patients.

After administration, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, worsening of colitis, and Crohn's disease have been reported. Less frequently, inflammation of the stomach wall (gastritis) has been observed.

As with other non-steroidal anti-inflammatory drugs, aseptic meningitis may occur, which can occur predominantly in patients with systemic lupus erythematosus or mixed connective tissue disease, and hematological reactions (purpura, aplastic anemia, and hemolytic anemia, and, more rarely, agranulocytosis and bone marrow hypoplasia).

Reporting of Adverse Effects

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

5. Storage of Difenadex

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

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

Store below 30°C.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines that you no longer need in the SIGRE Point of the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. In this way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Difenadex

The active ingredient is dexketoprofen trometamol. Each sachet of oral solution contains 36.9 mg of dexketoprofen trometamol, equivalent to 25 mg of dexketoprofen.

The other components are: ammonium glycyrrhizate, neohesperidin dihydrochalcone, methyl parahydroxybenzoate (E-218), sodium saccharin, sucrose, macrogol, lemon flavor (contains ethanol), povidone, anhydrous sodium hydrogen phosphate, sodium dihydrogen phosphate dihydrate, purified water.

Appearance of the Product and Package Contents

Transparent yellow-orange solution with a lemon-citrus odor, packaged in single-dose sachets of 10 ml.

It is presented in packages containing 10 sachets.

Marketing Authorization Holder:

Laboratorios Normon, S.A.

Ronda de Valdecarrizo, 6

Tres Cantos, 28760, Madrid

Manufacturer

SAG MANUFACTURING S.L.U.

Crta N-I, Km 36, San Agustín de Guadalix,

28750 Madrid

Spain

or

Galenicum Health, S.L.

Calle de San Gabriel 50

Pol Ind Esplugues de Llobregat

Esplugues de Llobregat,

08950 Barcelona

Spain

Date of the Last Revision of this Prospectus:March 2024

Other Sources of Information:

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es.