DifenadeX 25 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Difenadex 25 mg hard capsules

dexketoprofen

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you need advice or further information, consult your pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.
• You must consult a doctor if you worsen or do not improve after 4 days.

Contents of the leaflet

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

1. What Difenadex is and what it is used for

This medicine is an analgesic belonging to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs).

Difenadex is used in adults for the short-term symptomatic treatment of mild to moderate acute pain, such as muscle or joint pain (for example, back pain, sprains and acute injuries), menstrual pain, and dental pain.

2. What you need to know before taking Difenadex

Do not take Difenadex

• If you are allergic to dexketoprofen trometamol or to any of the other components of this medicine (listed in section 6);
• If you are allergic to acetylsalicylic acid or to any other non-steroidal anti-inflammatory drug (NSAID);
• If you have asthma or have experienced 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 previously experienced photoallergic or phototoxic reactions (a special type of redness or sunburn-like skin damage on sun-exposed skin) while taking ketoprofen (a non-steroidal anti-inflammatory drug) or fibrates (medicines used to reduce blood fat levels);
• If you have peptic ulcer, gastrointestinal bleeding, or have previously experienced bleeding, ulceration, or perforation of the stomach or intestine;
• If you have chronic digestive problems (e.g., indigestion, heartburn); if you have previously experienced gastrointestinal bleeding or perforation due to prior 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 renal impairment, or severe hepatic impairment;
• If you have bleeding disorders or blood coagulation disorders;
• If you are severely dehydrated (have lost a large amount of body fluid) due to vomiting, diarrhea, or insufficient fluid intake;
• If you are in the third trimester of pregnancy or during breastfeeding.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Difenadex:

• If you are allergic or have previously had allergic problems;
• If you have kidney, liver, or heart disease (hypertension and/or heart failure), fluid retention, or have previously had any of these conditions;
• If you are taking diuretics or have insufficient hydration and reduced blood volume due to excessive fluid loss (e.g., from excessive urination, diarrhea, or vomiting);
• If you have heart conditions, a history of stroke, or think you may be at risk of such conditions (e.g., you have high blood pressure, diabetes, high cholesterol, or are a smoker), you should discuss this treatment with your doctor or pharmacist. Medicines like Difenadex may be associated with a small increased risk of heart attacks (“myocardial infarction”) or strokes (“cerebrovascular accident”). 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 experience adverse 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 disorder affecting blood or blood cell production;
• If you have systemic lupus erythematosus or mixed connective tissue disease (immune system disorders affecting connective tissue);
• If you currently have or have previously had chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease);
• If you currently have or have previously had stomach or intestinal disorders;
• If you have an infection—see the section «Infections» below;
• If you are taking other medicines that increase the risk of peptic ulcer or bleeding, such as oral corticosteroids, certain antidepressants (SSRIs, Selective Serotonin Reuptake Inhibitors), or agents that prevent blood clotting such as acetylsalicylic acid (aspirin) or anticoagulants like warfarin. In such cases, consult your doctor before taking this medicine: your doctor may prescribe an additional medicine to protect your stomach (e.g., misoprostol or other drugs that block gastric acid production);
• If you have asthma, especially combined with chronic rhinitis or sinusitis, and/or nasal polyps, as you are at higher risk of being allergic to acetylsalicylic acid and/or NSAIDs than the general population. Administration of this medicine may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

Allergic reactions to dexketoprofen, including respiratory problems, swelling of the face and neck area (angioedema), and chest pain, have been reported. Immediately discontinue treatment with Difenadex and contact your doctor or nearest emergency service if you experience any of these symptoms.

Infections

• Difenadex may mask signs of infection, such as fever and pain. Therefore, this medicine may delay appropriate treatment of the infection, increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you take this medicine while having an infection and infection symptoms persist or worsen, consult a doctor immediately.
• Avoid using this medicine if you have chickenpox.

Children and adolescents

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

Other medicines and Difenadex

Inform your doctor or pharmacist if you are currently taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription. Some medicines should not be taken together, while others may require dose adjustments when used concurrently.

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

Combinations not recommended:

• Acetylsalicylic acid, corticosteroids, and other anti-inflammatory drugs;
• Warfarin, heparin, and other medicines used to prevent blood clotting;
• Lithium, used to treat certain mood disorders;
• Methotrexate (a cancer and immunosuppressant medicine), when used at high doses of 15 mg/week;
• Hydantoins and phenytoin, used for epilepsy;
• Sulfamethoxazole, used for bacterial infections;

Combinations requiring caution:

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

Combinations to be aware of:

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

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

Taking Difenadex with food and drink and alcohol

In general, it is recommended to take the medicine with food to reduce the possibility of causing stomach disturbances (see also section 3, “Method of administration”).

The use of NSAIDs in combination with alcohol may worsen 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.

Do not take this medicine during the last 3 months of pregnancy, as it may harm the fetus or cause problems during delivery. It may cause kidney and heart problems in your fetus. It may affect your tendency and your baby’s tendency to bleed and may delay or prolong labor beyond expected duration. You should not take this medicine during the first 6 months of pregnancy unless clearly necessary and as directed by your doctor. If treatment is needed during this period or while trying to become pregnant, you should take the lowest effective dose for the shortest possible time. From week 20 of pregnancy, this medicine may cause kidney problems in your fetus if taken for more than a few days, which may lead to low levels of amniotic fluid surrounding the baby (oligohydramnios). If treatment for more than a few days is needed, your doctor may recommend additional monitoring.

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine, as it may not be suitable for you.

Women planning pregnancy or who are pregnant should avoid using this medicine. Treatment at any stage of pregnancy should only occur under medical supervision.

The use of this medicine may impair fertility; therefore, its use is not recommended when trying to conceive or when being evaluated for infertility.

Driving and using machines

This medicine may slightly affect your ability to drive and use machines, as it may cause dizziness, drowsiness, or visual disturbances as adverse effects of treatment. If you experience these effects, do not operate machinery or drive until the symptoms have resolved. Seek advice from your doctor.

Excipients

This medicine contains less than 23 mg of sodium (1 mmol) per capsule; hence, it is essentially “sodium-free”.

3. How to take Difenadex

Follow exactly the instructions for use provided in this leaflet or those given by your doctor or pharmacist. If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

The required dose of the medicine may vary depending on the type, intensity, and duration of pain. The lowest effective dose should be used for the shortest duration necessary to relieve symptoms. If you have an infection, consult a doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Adults over 18 years of age

In general, the recommended dose is 1 capsule (25 mg of dexketoprofen) every 8 hours, not exceeding 3 capsules per day (75 mg).

Elderly patients or those with renal or hepatic impairment

If you are elderly or suffer from mild renal impairment or mild to moderate hepatic impairment, treatment should be initiated with a maximum of 2 capsules per day (50 mg) of dexketoprofen.

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

Dexketoprofen must not be used if you have moderate or severe renal impairment or severe hepatic impairment. Consult your doctor or pharmacist if you are unsure.

Use in children and adolescents

This medicine must not be used in children and adolescents (under 18 years of age).

Method of administration

Take the capsules with an adequate amount of water.

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

Duration of treatment

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

If you take more Difenadex than you should

Contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medicine and the amount taken. It is recommended to bring the medicine packaging and leaflet to the healthcare professional.

If you forget to take Difenadex

Do not take a double dose to make up for a missed dose. Take the next dose as scheduled (according to section 3 "How to take Difenadex").

If you have any 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 everyone will experience them.

The possible adverse effects are listed below according to their frequency. Since this list is partly based on adverse effects observed with oral tablet use, and Dexketoprofen trometamol capsules are absorbed faster than tablets, the actual frequency of adverse effects (gastrointestinal) may be higher with Dexketoprofen capsules. The following table indicates how many patients may experience these adverse effects:

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

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

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

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

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

Peptic ulcer, peptic ulcer perforation or bleeding (which may present as vomiting blood or black stools), fainting, high blood pressure, slow breathing, fluid retention and peripheral swelling (e.g., swollen ankles), laryngeal edema, loss of appetite (anorexia), abnormal sensation, itchy 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 (may affect up to 1 in 10,000 people)

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

Frequency unknown: frequency cannot be determined from available data

Chest pain, which may be a symptom of a potentially serious allergic reaction called Kounis syndrome.

Drug-induced fixed eruption

An allergic skin reaction known as drug-induced fixed eruption, which may include round or oval red patches and skin swelling, blisters, and itching. Darkening of the skin in affected areas may also occur, which can persist after healing. Drug-induced fixed eruption usually reappears in the same location or locations if the medicine is taken again.

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

Stop taking this medicine immediately if you develop a skin rash or lesions inside the mouth or on the genitals, or any other signs of allergy.

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

Medicines such as Difenadex may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke ("cerebrovascular accident").

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

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

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

As with other NSAIDs, hematological reactions may occur (purpura, aplastic and hemolytic anemia, and more rarely agranulocytosis and bone marrow hypoplasia).

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Difenadex

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging and on the blister, after EXP. The expiry date refers to the last day of the month indicated.

Store below 25°C.

Keep the blister in the outer packaging to protect it from light.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their packaging at the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Difenadex

• Each capsule contains 25 mg of dexketoprofen as dexketoprofen trometamol.

• Other components are:

• Capsule contents: Pregelatinized corn starch, microcrystalline cellulose, sodium carboxymethylstarch (Type A from potato), and glycerol distearate.

• Capsule composition (body and cap): Gelatin, titanium dioxide (E171), quinoline yellow (E104), and patent blue V (E131).

Appearance of the product and pack contents

Difenadex 25 mg hard capsules EFG are green hard gelatin capsules containing white or almost white crystalline powder.

The capsules are supplied in single-dose blisters made of Aluminum/PVC-ACLAR® (PCTFE) or Aluminum/PVC-PE-PVDC (90), each containing 10 hard capsules.

Marketing Authorization Holder and Manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6.

28760 Tres Cantos,

Madrid (Spain).

Date of the most recent review of this leaflet: September 2025

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products: http://www.aemps.gob.es