DIFENADOL RAPID 400 mg ORAL SOLUTION GRANULES

Introduction

Package Leaflet: Information for the User

Difenadol Rapid 400 mg Granules for Oral Solution

Ibuprofen (arginine)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Follow the instructions for administration of the medicine contained in this leaflet or as indicated by your doctor, pharmacist, or nurse.

• Keep this leaflet, as you may need to read it again.
• If you need advice or more information, consult your pharmacist.
• If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.
• You should consult a doctor if your symptoms worsen or do not improve, if the fever persists for more than 3 days or the pain for more than 5 days.

Contents of the Package Leaflet

1. What is Difenadol Rapid and what is it used for
2. What you need to know before taking Difenadol Rapid
3. How to take Difenadol Rapid
4. Possible side effects
5. Storage of Difenadol Rapid
6. Contents of the pack and further information

1. What is Difenadol Rapid and what is it used for

Ibuprofen, the active ingredient of this medicine, acts by reducing pain and fever.

This medicine is used in adults and adolescents from 12 years old (weight equal to or greater than 40 kg), for the symptomatic relief of occasional mild to moderate pain, such as headaches, dental pain, menstrual pain, muscle pain (cramps) or back pain (lumbago), as well as in febrile states.

2. What you need to know before taking Difenadol Rapid

Do not take Difenadol Rapid

• If you are allergic (hypersensitive) to ibuprofen, other non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or any of the other components of this medicine (listed in section 6). Allergic reactions may include: skin rash with itching, swelling of the face, lips, or tongue, nasal discharge, difficulty breathing, bronchospasm, or asthma.
• If you have a severe liver or kidney disease.
• If you have had a stomach or duodenal ulcer or have suffered a perforation of the digestive tract.
• If you vomit blood.
• If you have black stools or bloody diarrhea.
• If you have an active cerebral hemorrhage or other active bleeding.
• If you have bleeding disorders or blood coagulation disorders, or are taking anticoagulants (medicines used to "thin" the blood). If it is necessary to use anticoagulant medications at the same time, your doctor will perform blood coagulation tests.
• If you have severe heart failure.
• If you have severe dehydration caused by vomiting, diarrhea, or insufficient fluid intake.
• If you are in the third trimester of pregnancy.

Warnings and Precautions

Anti-inflammatory/analgesic medicines like ibuprofen may be associated with a small increased risk of heart attack or stroke, especially when used in high doses. Do not exceed the recommended dose or treatment duration. Do not take more than 3 sachets of granules (1200 mg of ibuprofen) per day, to avoid the possible appearance of circulatory or heart problems.

Tell your doctor

• If you have edema (fluid retention).
• If you have or have had heart disorders or high blood pressure.
• If you have asthma or any other respiratory disorder.
• If you have an infection, Difenadol Rapid 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.
• If you have kidney or liver disease, are over 60 years old, or need to take the medicine for a prolonged period (more than 1 to 2 weeks), your doctor may need to perform regular checks. Your doctor will indicate the frequency of these checks.
• If you experience symptoms of dehydration, e.g., severe diarrhea or vomiting, take plenty of fluids and contact your doctor immediately, as ibuprofen in this case could cause kidney failure due to dehydration.
• If you have had or developed an ulcer, bleeding, or perforation in the stomach or duodenum, which may be manifested by intense or persistent abdominal pain and/or black stools, or even without previous warning symptoms. This risk is higher when using high doses and prolonged treatments, in patients with a history of peptic ulcer, and in elderly patients. In these cases, your doctor will consider the possibility of associating a stomach-protecting medicine.
• If you take anticoagulant medications, such as oral anticoagulants, antiplatelet agents of the aspirin type. You should also discuss the use of other medications that may increase the risk of such bleeding, such as corticosteroids and selective serotonin reuptake inhibitor antidepressants.
• If you have Crohn's disease (a chronic disease in which the immune system attacks the intestine, causing inflammation that usually produces bloody diarrhea) or ulcerative colitis, as medicines like Difenadol Rapid may worsen these conditions.
• If you are being treated with diuretics (medicines to urinate), as your doctor should monitor your kidney function.
• If you have systemic lupus erythematosus (a chronic disease that affects the immune system and can affect various vital organs, the nervous system, blood vessels, skin, and joints), as it may cause aseptic meningitis (inflammation of the meninges that protect the brain and spinal cord, not caused by bacteria).
• If you have acute intermittent porphyria (a metabolic disease that affects your blood and can cause symptoms such as reddish urine color, blood in urine, or liver disease), so that your doctor can assess the convenience or not of treatment with ibuprofen.
• If you experience headaches after prolonged treatment, do not take higher doses of the medicine.
• If you experience vision changes during treatment with ibuprofen, discontinue treatment and consult your doctor for an ophthalmological examination.
• It is possible that allergic reactions may occur with this medicine. Treatment should be discontinued if redness and inflammation or skin lesions appear.
• Skin reactions: Serious skin reactions have been reported with ibuprofen (arginine) treatment. Stop taking this medicine and consult your doctor immediately if you experience any skin rash, mucous membrane lesions, blisters, or other signs of allergy, as these may be the first signs of a very serious skin reaction. See section 4.
• Your doctor will perform stricter monitoring if you receive ibuprofen after undergoing major surgery.
• It is advisable not to take this medicine if you have chickenpox.
• Ibuprofen has been reported to cause signs of an allergic reaction to this medicine, including breathing difficulties, swelling of the face and neck area (angioedema), and chest pain. Discontinue treatment with ibuprofen immediately and contact your doctor or emergency medical services as soon as possible if you observe any of these signs.

It is important to use the smallest dose that relieves-controls the pain and not to take this medicine for longer than necessary to control your symptoms.

Avoid concomitant administration with other NSAIDs, including COX-2 inhibitors.

Precautions in Elderly Patients

Elderly patients have a higher frequency of adverse reactions to NSAIDs (non-steroidal anti-inflammatory drugs), especially gastrointestinal bleeding and perforation, which can be fatal.

Cardiovascular precautions

Anti-inflammatory/analgesic medicines like ibuprofen may be associated with a small increased risk of heart attack or stroke, especially when used in high doses. Do not exceed the recommended dose or treatment duration.

You should discuss your treatment with your doctor or pharmacist before taking Difenadol Rapid if:

• You have heart problems, including heart failure, angina (chest pain), or if you have had a heart attack, bypass surgery, peripheral arteriopathy (circulation problems in the legs or feet due to narrowing or blockage of the arteries), or any type of stroke (including a "mini-stroke" or transient ischemic attack "TIA").
• You have high blood pressure, diabetes, high cholesterol, have a family history of heart disease or stroke, or are a smoker.

Similarly, these types of medicines can cause fluid retention, especially in patients with heart failure and/or high blood pressure (hypertension).

Respiratory Disorders

Ibuprofen should be used with caution when administered to patients who have or have a history of bronchial asthma, chronic rhinitis, or allergic diseases, as ibuprofen has been reported to cause bronchospasm, urticaria, or angioedema in these patients.

Severe Adverse Skin Reactions (SASR)

Severe skin reactions have been reported, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), in association with ibuprofen treatment. Discontinue treatment with Difenadol Rapid and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Children and Adolescents

There is a risk of kidney failure in dehydrated children and adolescents.

This medicine is not recommended for use in children and adolescents weighing less than 40 kg or under 12 years old, as the dose of ibuprofen it contains is not suitable for the recommended dosage in this group of patients.

Precautions during Pregnancy and in Women of Childbearing Age

Because the administration of ibuprofen-type medicines has been associated with an increased risk of congenital anomalies/abortions, their administration is not recommended during the first and second trimesters of pregnancy unless strictly necessary and advised by your doctor.

If you need treatment during this period or while trying to become pregnant, you should use the lowest dose for the shortest possible time.

If you take it for a few days from the 20th week of gestation onwards, Difenadol Rapid may cause kidney problems in your baby, which can lead to low levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby's heart. If you need treatment for a few more days, your doctor may recommend additional monitoring.

In the third trimester, the administration of ibuprofen is contraindicated.

For women of childbearing age, it should be noted that ibuprofen-type medicines have been associated with a decrease in fertility.

Interference with Laboratory Tests

• Bleeding time (may be prolonged for 1 day after discontinuing treatment)
• Blood glucose concentration (may decrease)
• Creatinine clearance (may decrease)
• Hematocrit or hemoglobin (may decrease)
• Blood urea nitrogen and serum creatinine and potassium concentrations (may increase)
• With liver function tests: increased transaminase values

If you are going to undergo any diagnostic test (including blood tests, urine tests, skin tests using allergens, etc.), inform your doctor that you are taking this medicine, as it may alter the results.

Other Medicines and Difenadol Rapid

Tell your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine.

Difenadol Rapid may affect or be affected by other medicines. For example:

• Anticoagulant medicines (e.g., to treat coagulation problems/prevent coagulation, e.g., aspirin, warfarin, ticlopidine)
• Medicines that lower high blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, and angiotensin-II receptor antagonists such as losartan)

The following medicines may interfere and should not be taken with Difenadol Rapid without consulting your doctor:

• Aspirin or other anti-inflammatory/analgesic agents: increase the risk of gastrointestinal ulcers and bleeding
• Antihypertensives (beta-blockers, ACE inhibitors, and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effect of diuretics and other antihypertensive substances. Concomitant administration of ibuprofen and potassium-sparing diuretics may cause hyperkalemia and increase the risk of kidney toxicity
• Antiplatelet agents (prevent the formation of blood clots or thrombi in blood vessels) such as ticlopidine
• Anticoagulants (medicines used to "thin" the blood) such as warfarin
• Lithium (medicine used to treat depression). Your doctor may adjust the dose of this medicine
• Methotrexate (for cancer and inflammatory diseases). Your doctor may adjust the dose of this antimetabolite medicine (slows down the growth of certain cells produced by the body)
• Mifepristone (inducer of abortions)
• Digoxin and cardiac glycosides (used in the treatment of heart disorders)
• Hydantoins such as phenytoin (used in the treatment of epilepsy)
• Sulfonamides such as sulfamethoxazole and cotrimoxazole (used in the treatment of certain bacterial infections)
• Corticosteroids such as cortisone and prednisolone
• Pentoxifylline (for intermittent claudication)
• Probenecid (used in patients with gout or with penicillin in infections)
• Antibiotics of the quinolone group such as norfloxacin
• Sulfinpyrazone (for gout)
• Sulfonylureas such as tolbutamide or insulin (for diabetes), may need to adjust the dose
• Certain antidepressants (selective serotonin reuptake inhibitors)
• Tacrolimus (used in organ transplants to prevent rejection)
• Zidovudine (medicine against the AIDS virus)
• Thrombolytics (medicines that dissolve blood clots)
• Aminoglycoside antibiotics such as neomycin
• Ginkgo biloba tree extracts
• CYP2C9 inhibitors (responsible for the metabolism of numerous drugs in the liver), such as voriconazole and fluconazole (used to treat fungal infections)

Other medicines may also affect or be affected by treatment with Difenadol Rapid. Therefore, you should always consult your doctor or pharmacist before using Difenadol Rapid with other medicines.

Taking Difenadol Rapid with Food, Drinks, and Alcohol

Take this medicine with meals or with milk.

Do not administer ibuprofen with alcohol to avoid damaging the stomach. Alcohol consumption during treatment may increase the risk of gastrointestinal adverse reactions.

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Difenadol Rapid should not be taken during pregnancy, especially during the third trimester (see section precautions during pregnancy and in women of childbearing age). It may cause kidney and heart problems in your baby. It may affect your and your baby's tendency to bleed and make labor longer than expected.

Minimal amounts of ibuprofen and its degradation products are excreted in breast milk. As no adverse effects are known in the infant, it is not usually necessary to interrupt breastfeeding during short-term use at recommended doses.

Therefore, if you become pregnant or are breastfeeding, consult your doctor.

Driving and Using Machines

If you experience dizziness, vertigo, vision changes, or other symptoms while taking this medicine, you should not drive or use hazardous machinery. If you only take one dose of ibuprofen or for a short period, it is not necessary to take special precautions.

Difenadol Rapid contains Aspartame, Sucrose, and Sodium

This medicine contains 20 mg of aspartame in each sachet. Aspartame is a source of phenylalanine, which may be harmful in case of phenylketonuria (PKU), a rare genetic disease in which phenylalanine accumulates due to the body's inability to eliminate it correctly.

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

It may cause cavities.

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

It may cause cavities.

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

3. How to take Difenadol rapid

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

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

The recommended dose is:

• Adults and adolescents from 12 years old (weight equal to or greater than 40 kg):Take one sachet (400 mg of ibuprofen) every 6 or 8 hours, if necessary.

No more than 3 sachets (1200 mg of ibuprofen) should be taken in 24 hours.

• Elderly patients:the dose must be established by the doctor, as it may be necessary to reduce the usual dose.
• Patients with kidney, liver, or heart disease:Reduce the dose and consult a doctor.

The administration of this medicine is subject to the appearance of pain or fever. As these disappear, the medication should be suspended.

You should consult a doctor if it worsens or does not improve, if the fever persists for more than 3 days or the pain for more than 3 days in adolescents or 5 days in adults.

Use in children

The use of this medicine is not recommended in children and adolescents with less than 40 kg of weight or under 12 years, as the dose of ibuprofen it contains is not suitable for the recommended posology in this group of patients.

Method of administration:

This medicine is administered orally.

Dissolve the contents of one sachet completely in a glass of water and ingest it afterwards. Take this medicine with meals or with milk, especially if digestive discomfort is noticed.

If you take more Difenadol rapid than you should

In case of overdose or accidental ingestion, consult immediately with a doctor or pharmacist or call the Toxicology Information Service (telephone: 91 562 04 20), indicating the medicine and the amount ingested or go to the nearest hospital to find out about the risk and ask for advice on the measures to be taken.

Symptoms of overdose may include nausea, stomach pain, vomiting (which may contain bloody sputum), gastrointestinal bleeding (see also section 4 below), diarrhea, dizziness, spasms, hypotension, or depression of the nervous system (reduction of consciousness) headache, ringing in the ears, confusion, and involuntary eye movement.

Nervousness, drowsiness, disorientation, or coma may also occur. Occasionally, patients develop seizures.

At high doses, symptoms of drowsiness, chest pain, palpitations, loss of consciousness, seizures (mainly in children), weakness, and dizziness, blood in the urine, low potassium levels in the blood, chills, and breathing problems have been reported.

In cases of significant overdose, renal failure and liver damage may occur.

Also, the prothrombin time/INR may be prolonged, probably due to interference with the action of circulating coagulation factors. Acute renal failure and liver damage may appear. It is possible that asthma may worsen in asthmatic patients. There is also a possibility that low blood pressure and reduced breathing may occur.

In case of ingestion of significant amounts, activated charcoal should be administered. Gastric lavage will be considered if large amounts have been ingested and within 60 minutes after ingestion.

If you forget to take Difenadol rapid

Do not take a double dose to make up for forgotten doses.

If you forget to take your corresponding dose, take it as soon as you remember. However, if the time of the next dose is very close, skip the forgotten dose and take the next dose at its usual time.

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

4. Possible adverse effects

Like all medicines, Difenadol rapid can have adverse effects, although not all people suffer from them. The adverse effects of medicines like Difenadol rapid are more common in people over 65 years old.

The incidence of adverse effects is lower in short treatments and if the daily dose is below the maximum recommended dose.

Frequencies are established according to the following classification: very frequent (may affect more than 1 in 10 patients); frequent (may affect up to 1 in 10 patients); infrequent (may affect up to 1 in 100 patients); rare (may affect up to 1 in 1,000 patients); very rare (may affect up to 1 in 10,000 patients); frequency not known (cannot be estimated from available data).

The following adverse effects have been observed:

Infections and infestations

Very rare:Exacerbation of inflammation-related infections (e.g., development of necrotizing fasciitis), coinciding with the use of non-steroidal anti-inflammatory drugs.

Note:If signs of infection or worsening are observed during treatment with ibuprofen, it is recommended to go to the doctor immediately, in case it is necessary to initiate anti-infective/antibiotic therapy.

Blood and lymphatic system disorders

Rare:Aplastic anemia (insufficiency of the bone marrow to produce different types of cells).

Very rare:Decreased platelets, decreased white blood cells (may manifest as frequent infections with fever, chills, or sore throat), decreased red blood cells (may manifest as difficulty breathing and paleness of the skin), decreased granulocytes (a type of white blood cell that can predispose to infections), pancytopenia (deficiency of red, white, and platelet cells in the blood), agranulocytosis (very large decrease in granulocytes), hemolytic anemia (premature destruction of red blood cells). The first symptoms are: fever, sore throat, superficial ulcers in the mouth, pseudo-flu symptoms, extreme fatigue, nasal and skin bleeding. Prolongation of bleeding time.

Immune system disorders

Infrequent:Allergic reaction, hypersensitivity reactions with skin rash and itching, as well as asthma attacks (possibly along with a drop in blood pressure).

Rare:Anaphylaxis (generalized allergic reaction).

Very rare:Severe hypersensitivity reactions (these can be characterized by swelling of the face, tongue, and larynx with bronchospasm, dyspnea, tachycardia, and hypotension that can include potentially fatal shock).

Note:In the event of these symptoms, which can occur with the first use, immediate medical attention is required.

Psychiatric disorders

Infrequent:Insomnia, anxiety, restlessness.

Rare:Psychotic reaction, nervousness, irritability, depression, confusion, disorientation.

Nervous system disorders

Frequent:Fatigue or drowsiness, headache, and dizziness or feeling of instability.

Infrequent:Insomnia, excitement, irritability.

Rare:Paresthesia (sensation of numbness, tingling, prickling, etc., more frequent in hands, feet, arms, or legs).

Very rare:Aseptic meningitis. In most cases where aseptic meningitis has been reported with ibuprofen, the patient suffered from some form of autoimmune disease (such as systemic lupus erythematosus or other collagen diseases), which was a risk factor. The symptoms of aseptic meningitis observed were neck stiffness, headache, nausea, vomiting, fever, or disorientation.

Eye disorders

Infrequent:Vision disturbances.

Rare:Abnormal or blurred vision.

Frequency not known:Papilledema (inflammation of the optic nerve).

Ear and labyrinth disorders

Frequent:Vertigo.

Infrequent:Ringing or buzzing in the ears.

Rare:Hearing difficulty.

Cardiac disorders

Medicines like Difenadol rapid may be associated with a moderate increase in the risk of suffering a heart attack ("myocardial infarction") or stroke.

Very rare:Palpitations, heart failure.

Frequency not known:Chest pain, which can be a sign of a potentially serious allergic reaction called Kounis syndrome.

Vascular disorders

Edema (fluid retention), arterial hypertension, and heart failure have also been observed in association with treatments with ibuprofen (arginine) medications.

Very rare:Arterial hypertension.

Frequency not known:Arterial thrombosis.

Respiratory disorders

Infrequent:Asthma, worsening of asthma, bronchospasm, dyspnea (breathing difficulty).

Frequency not known:Throat irritation.

Gastrointestinal disorders

The most frequent adverse effects that occur with medicines like Difenadol rapid are gastrointestinal: peptic ulcers, gastrointestinal bleeding, perforations (in some cases fatal), especially in elderly patients.

Frequent:Gastrointestinal discomfort such as heartburn (acidity, reflux), abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, and mild gastrointestinal bleeding that can cause anemia in exceptional cases.

Infrequent:Gastrointestinal ulcers, potentially with bleeding and perforation, ulcerative stomatitis, exacerbation of colitis and Crohn's disease, melena (blood in stool), gastritis.

Rare:Vomiting blood.

Very rare:Esophageal inflammation, pancreatitis, intestinal stenosis.

Frequency not known:Anorexia.

Hepatobiliary disorders

Rare:Liver damage, hepatitis (inflammation of the liver), liver function abnormalities, and jaundice (yellowing of the skin and eyes).

Skin and subcutaneous tissue disorders

Frequent:Skin rash.

Infrequent:Redness of the skin, itching or swelling of the skin (angioedema, urticaria), purpura (purple spots on the skin).

Rare:Anaphylactic reaction

Very rare:Ibuprofen (arginine) medications may be associated, in very rare cases, with severe blistering reactions such as Stevens-Johnson syndrome (widespread erosions affecting the skin and two or more mucous membranes and lesions of purple color, preferably on the trunk) and toxic epidermal necrolysis (erosions on mucous membranes and painful lesions with necrosis and shedding of the epidermis). Hair loss, erythema multiforme (skin lesion), exceptionally severe skin infections and soft tissue complications may occur during chickenpox.

Frequency not known:Skin reactions due to light influence (photosensitivity), worsening of skin reactions. A severe skin reaction known as DRESS syndrome may occur. The symptoms of DRESS syndrome include: skin rash, lymph node inflammation, and elevated eosinophils (a type of white blood cell). Generalized red scaly rash, with bumps under the skin and blisters located mainly in skin folds, trunk, and upper limbs, accompanied by fever at the start of treatment (acute generalized exanthematous pustulosis). Stop taking Difenadol rapid if you present these symptoms and seek immediate medical attention. See also section 2.

Renal and urinary disorders

Rare:Hematuria (presence of blood in the urine).

Very rare:Edema (signs that may be indicative of kidney disease, which can sometimes include kidney failure); renal tissue damage (papillary necrosis), increased serum uric acid concentration.

Based on experience with non-steroidal anti-inflammatory drugs in general, cases of interstitial nephritis, nephrotic syndrome, and kidney failure cannot be excluded.

General disorders

Very rare:Worsening of inflammation during infectious processes.

Frequency not known:Edema.

Complementary tests

Rare:Alteration of liver function tests.

Frequency not known:Alteration of renal function tests.

To date, no serious allergic reactions have been reported with Difenadol rapid, although they cannot be ruled out. The manifestations of this type of effect could be fever, skin rash, abdominal pain, intense and persistent headache, nausea, vomiting, angioedema, swelling of the face, tongue, and throat, breathing difficulty, asthma, palpitations, hypotension, or shock.

If any of the following adverse effects appear, interrupt treatment and go immediately to your doctor:

• Allergic reactions such as skin rashes, swelling of the face, wheezing in the chest, or breathing difficulty.
• Vomiting blood or coffee grounds-like material.
• Blood in the stool or bloody diarrhea.
• Severe stomach pain.
• Blistering or significant skin peeling.
• Severe or persistent headache.
• Yellowing of the skin (jaundice).
• Signs of severe hypersensitivity (see above in this section).
• Swelling of the limbs or fluid accumulation in the arms or legs.
• Visual disturbances.

Interrupt treatment with ibuprofen and seek immediate medical attention if you notice any of the following symptoms:

• Red, non-elevated, target-shaped or circular spots on the trunk, often with blisters in the center, skin peeling, mouth, throat, nose, genital, and eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].
• Generalized skin rash, elevated body temperature, and swollen lymph nodes (DRESS syndrome).
• Generalized red scaly rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the start of treatment (acute generalized exanthematous pustulosis).

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 does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Difenadol rapid

Keep this medicine out of sight and reach of children.

No special storage conditions are required. Keep in the original packaging to protect from light and moisture.

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

Medicines should not be thrown down the drain or into the trash. Deposit the packaging and medicines that are no longer needed in the SIGRE point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This way, you will help protect the environment.

6. Content of the packaging and additional information

Composition of Difenadol rapid

• The active ingredient is ibuprofen. Each sachet contains 400 mg of ibuprofen equivalent to 740 mg of ibuprofen (arginine).
• The other components (excipients) are L-arginine, aspartame (E-951), sucrose, sodium hydrogen carbonate, sodium saccharin, sodium lauryl sulfate, orange flavor (contains glucose in maltodextrin from corn and other excipients), and purified water.

Appearance of Difenadol rapid and packaging content

White granulate with characteristic orange odor.

It is presented in packages with 12 or 20 paper/aluminum sealed sachets.

Marketing authorization holder and manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (Spain)

Date of the last revision of this prospectus:January 2025

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