Difenadol Rapid 400 mg granules for oral solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Difenadol rapid 400 mg granules for oral solution

Ibuprofen (arginine)

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

Follow exactly the instructions for administration of the medicine contained in this leaflet or those 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 any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.
• You should consult a doctor if you worsen or do not improve, if fever persists for more than 3 days, or if pain lasts for more than 5 days.

Leaflet contents

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

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

Ibuprofen, the active substance in this medicine, works by reducing pain and fever.

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

2. What you need to know before taking Difenadol rapid

Do not take Difenadol rapid

• If you are allergic (hypersensitive) to ibuprofen, to other medicines in the group of non-steroidal anti-inflammatory drugs (NSAIDs), to aspirin, or to any of the other components of this medicine (listed in section 6). Signs of allergy may include: itchy skin rash, swelling of the face, lips or tongue, runny nose, breathing difficulties, bronchospasm or asthma.
• If you have severe liver or kidney disease.
• If you have had a stomach or duodenal ulcer or bleeding, or have experienced a gastrointestinal perforation.
• If you are vomiting blood.
• If you have black stools or bloody diarrhoea.
• If you have active cerebral haemorrhage or any other active bleeding.
• If you have bleeding or blood coagulation disorders, or are taking anticoagulants (medicines used to "thin" the blood). If anticoagulants must be used simultaneously, your doctor will perform blood coagulation tests.
• If you have severe heart failure.
• If you have severe dehydration caused by vomiting, diarrhoea or insufficient fluid intake.
• If you are in the third trimester of pregnancy.

Warnings and precautions

Medicines such as ibuprofen, which are anti-inflammatory/analgesic, may be associated with a small increased risk of heart attack or stroke, especially when used at high doses. Do not exceed the recommended dose or duration of treatment. Do not take more than 3 sachets of granules (1,200 mg of ibuprofen) per day, to avoid possible circulatory or heart problems.

Tell your doctor

• If you have oedema (fluid retention).
• If you have or have had heart problems or high blood pressure.
• If you suffer from asthma or any other respiratory disorder.
• If you have an infection, Difenadol rapid 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.
• If you have kidney or liver disease, are over 60 years old, or need to take the medicine long-term (more than 1–2 weeks), your doctor may need to perform regular monitoring. Your doctor will advise you on how often these checks should be done.
• If you experience symptoms of dehydration, e.g. severe diarrhoea or vomiting, drink plenty of fluids and contact your doctor immediately, as ibuprofen in such cases could lead to renal failure due to dehydration.
• If you have had or develop a stomach or duodenal ulcer, bleeding or perforation, which may present as severe or persistent abdominal pain and/or black stools, or even without prior warning symptoms. This risk is higher when high doses or prolonged treatment are used, in patients with a history of peptic ulcer, and in elderly patients. In such cases, your doctor may consider adding a stomach-protective medicine.
• If you are taking medicines that affect blood coagulation, such as oral anticoagulants or antiplatelet agents like acetylsalicylic acid. You should also mention the use of other medicines that could increase the risk of such bleeding, such as corticosteroids and selective serotonin reuptake inhibitor (SSRI) antidepressants.
• If you have Crohn's disease (a chronic condition in which the immune system attacks the intestine, causing inflammation that usually results in bloody diarrhoea) or ulcerative colitis, as medicines like Difenadol rapid may worsen these conditions.
• If you are taking diuretics (medicines to increase urination), because your doctor needs to monitor your kidney function.
• If you have systemic lupus erythematosus (a chronic disease affecting the immune system that may affect vital organs, the nervous system, blood vessels, skin and joints), as aseptic meningitis (inflammation of the meninges, the membranes protecting the brain and spinal cord, not caused by bacteria) may occur.
• If you have acute intermittent porphyria (a metabolic disorder affecting the blood that may cause symptoms such as reddish urine, blood in urine or liver disease), so your doctor can assess whether treatment with ibuprofen is appropriate.
• If you suffer from headaches after prolonged treatment, do not take higher doses of the medicine.
• If you experience vision disturbances during treatment with ibuprofen, stop the treatment and consult your doctor for an ophthalmological examination.
• Allergic reactions may occur with this medicine. Discontinue treatment if redness, inflammation or skin lesions appear.
• Skin reactions: Serious skin reactions have been reported with ibuprofen (arginia). Stop taking this medicine and see a doctor immediately if you develop any skin rash, mucosal lesions, blisters or other signs of allergy, as these may be early signs of a very serious skin reaction. See section 4.
• Your doctor will perform stricter monitoring if you receive ibuprofen after major surgery.
• It is advisable not to take this medicine if you have chickenpox.
• Signs of an allergic reaction to ibuprofen have been reported, including breathing difficulties, facial and neck swelling (angioedema), and chest pain. Immediately stop treatment with ibuprofen and contact your doctor or emergency medical services as soon as possible if you notice any of these signs.

It is important to use the lowest effective dose that relieves/controls your pain and not to take this medicine 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 such as ibuprofen may be associated with a small increased risk of heart attack or stroke, particularly when used at high doses. Do not exceed the recommended dose or duration of treatment.

Discuss your treatment with your doctor or pharmacist before taking Difenadol rapid if:

• You have heart problems, including heart failure, angina (chest pain), or have had a heart attack, coronary bypass surgery, peripheral arterial disease (circulation problems in legs or feet due to narrowed or blocked arteries), or any type of stroke (including a "mini-stroke" or transient ischaemic attack "TIA").
• You have high blood pressure, diabetes, high cholesterol, a family history of heart disease or stroke, or if you smoke.

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

Respiratory disorders

Ibuprofen should be used with caution in 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 such patients.

Serious cutaneous adverse reactions (SCARs)

Serious 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. Stop treatment with Difenadol rapid and seek immediate medical attention if you notice any symptoms related to these serious skin reactions described in section 4.

Children and adolescents

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

The use of this medicine is not recommended in children and adolescents weighing less than 40 kg or under 12 years of age, as the ibuprofen dose it contains is not suitable for the recommended dosing in this patient group.

Pregnancy and fertility precautions

Because administration of medicines like ibuprofen has been associated with an increased risk of congenital malformations or miscarriage, their use is not recommended during the first and second trimesters of pregnancy unless strictly necessary and advised by your doctor.

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

If taken for several days from 20 weeks of gestation onwards, Difenadol rapid may cause kidney problems in your baby, which may 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 longer treatment is needed, your doctor may recommend additional monitoring.

In the third trimester, administration of ibuprofen is contraindicated.

For women of childbearing age, it should be noted that medicines like ibuprofen have been associated with reduced fertility.

Interference with laboratory tests

• Bleeding time (may be prolonged for up to 1 day after stopping treatment)
• Blood glucose concentration (may decrease)
• Creatinine clearance (may decrease)
• Haematocrit or haemoglobin (may decrease)
• Blood urea nitrogen levels and serum creatinine and potassium concentrations (may increase)
• Liver function tests: increased transaminase values

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

Other medicines and Difenadol rapid

Inform your doctor or pharmacist if you are currently using, have recently used, or might need to use any other medicines.

Difenadol rapid may interact with or be affected by other medicines. For example:

• Anticoagulant medicines (e.g. to treat or prevent blood clotting, e.g. acetylsalicylic acid, warfarin, ticlopidine).
• Medicines that lower high blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, angiotensin-II receptor antagonists such as losartan).

The following medicines may interact and therefore should not be taken together with Difenadol rapid without first consulting your doctor:

• Acetylsalicylic acid 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 agents. Concomitant administration of ibuprofen and potassium-sparing diuretics may cause hyperkalaemia and increase the risk of renal toxicity.
• Antiplatelet agents (prevent blood clots in blood vessels) such as ticlopidine.
• Anticoagulants (medicines used to "thin" the blood and prevent clots) such as warfarin.
• Lithium (a medicine used to treat depression). Your doctor may adjust the dose of this medicine.
• Methotrexate (used to treat cancer and inflammatory diseases). Your doctor may adjust the dose of this antimetabolite medicine (which slows the growth of certain body cells).
• Mifepristone (abortion-inducing agent).
• Digoxin and cardiac glycosides (used to treat heart disorders).
• Hydantoins such as phenytoin (used to treat epilepsy).
• Sulphonamides such as sulfamethoxazole and cotrimoxazole (used to treat certain bacterial infections).
• Corticosteroids such as cortisone and prednisolone.
• Pentoxifylline (used to treat intermittent claudication).
• Probenecid (used in gout patients or with penicillin for infections).
• Quinolone antibiotics such as norfloxacin.
• Sulfinpyrazone (for gout).
• Sulfonylureas such as tolbutamide or insulin (for diabetes); dose adjustment may be necessary.
• Certain antidepressants (serotonin reuptake inhibitors).
• Tacrolimus (used in organ transplants to prevent rejection).
• Zidovudine (an anti-HIV medicine).
• Thrombolytics (medicines that dissolve blood clots).
• Aminoglycoside antibiotics such as neomycin.
• Herbal extracts: Ginkgo biloba.
• 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, 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 food or milk.

Do not take ibuprofen with alcohol, to avoid stomach damage. 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 on pregnancy and fertility precautions). It may cause kidney and heart problems in your baby. It may affect your tendency and your baby's tendency to bleed and may make labour later or longer than expected.

Minimal amounts of ibuprofen and its metabolites are excreted in breast milk. As no adverse effects in infants are known, breastfeeding usually does not need to be interrupted 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 disturbances or other symptoms while taking this medicine, you should not drive or operate dangerous machinery. If you take only a single dose of ibuprofen or use it for a short period, special precautions are generally not required.

Difenadol rapid contains aspartame, sucrose and sodium

This medicine contains 20 mg of aspartame per sachet. Aspartame contains a source of phenylalanine, which may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

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

It may cause dental caries.

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

It may cause dental caries.

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

3. How to take Difenadol rapid

Follow exactly the instructions for use provided in this leaflet or those given by your doctor, pharmacist, or nurse. If in doubt, consult your doctor, pharmacist, or nurse.

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

Recommended dose:

• Adults and adolescents aged 12 years and older (weight equal to or greater than 40 kg): Take one sachet (400 mg of ibuprofen) every 6 or 8 hours, as needed.

Do not exceed 3 sachets (1,200 mg of ibuprofen) in 24 hours.

• Elderly patients: The dose should be determined by the doctor, as a reduction from the usual dose may be necessary.
• Patients with kidney, liver, or heart disease: Reduce the dose and consult your doctor.

This medicine should only be taken when pain or fever occurs. As these symptoms subside, treatment should be discontinued.

Consult a doctor if your condition worsens or does not improve, if fever persists for more than 3 days, or if pain lasts more than 3 days in adolescents or 5 days in adults.

Use in children

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

Method of administration:

This medicine is administered orally.

Completely dissolve the contents of one sachet in a glass of water and take immediately. Take this medicine with food or milk, especially if gastrointestinal discomfort occurs.

If you take more Difenadol rapid than you should

In case of overdose or accidental ingestion, immediately consult 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 learn about the risks and receive advice on the necessary measures.

Symptoms of overdose may include nausea, stomach pain, vomiting (which may contain blood-stained sputum), gastrointestinal bleeding (see also section 4 below), diarrhea, dizziness, spasms, hypotension, or signs of central nervous system depression (reduced consciousness), headache, tinnitus, confusion, and involuntary eye movements.

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

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

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

Additionally, prothrombin time/INR may be prolonged, likely due to interference with circulating coagulation factors. Acute renal failure and liver damage may occur. Asthma may worsen in asthmatic patients. Low blood pressure and reduced respiration are also possible.

In cases of ingestion of large quantities, activated charcoal should be administered. Gastric emptying should be considered if large amounts have been ingested and within 60 minutes of ingestion.

If you forget to take Difenadol rapid

Do not take a double dose to make up for a missed dose.

If you forget to take your dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take the next dose at the usual time.

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

4. Possible adverse effects

Like all medicines, Difenadol rapid may have adverse effects, although not everyone will experience them. Adverse effects of medicines such as Difenadol rapid are more common in people over 65 years of age.

The incidence of adverse effects is lower with short-term treatment and when the daily dose is below the recommended maximum dose.

Frequencies are defined according to the following classification: very common (may affect more than 1 in 10 patients); common (may affect up to 1 in 10 patients); uncommon (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 to infection (e.g., development of necrotizing fasciitis), coinciding with the use of non-steroidal anti-inflammatory drugs.

Note: If signs of infection appear or worsen during treatment with ibuprofen, consult a doctor immediately, as anti-infective/antibiotic therapy may be required.

Blood and lymphatic system disorders

Rare: Aplastic anemia (failure of the bone marrow to produce various types of blood cells).

Very rare: Decreased platelet count, decreased white blood cells (may manifest as frequent infections with fever, chills, or sore throat), decreased red blood cells (may manifest as shortness of breath and pale skin), decreased granulocytes (a type of white blood cell that may increase susceptibility to infections), pancytopenia (deficiency of red blood cells, white blood cells, and platelets in the blood), agranulocytosis (severe reduction in granulocytes), hemolytic anemia (premature destruction of red blood cells). Initial symptoms include: fever, sore throat, superficial mouth ulcers, flu-like symptoms, extreme fatigue, nosebleeds, and skin bleeding. Prolonged bleeding time.

Immune system disorders

Uncommon: Allergic reaction, hypersensitivity reactions with skin rash and pruritus, as well as asthma attacks (possibly accompanied by a drop in blood pressure).

Rare: Anaphylaxis (generalized allergic reaction).

Very rare: Severe hypersensitivity reactions (these may be characterized by swelling of the face, tongue, and larynx with bronchospasm, dyspnea, tachycardia, and hypotension, which may include potentially life-threatening shock).

Note: If these symptoms occur, even with first use, immediate medical attention is required.

Psychiatric disorders

Uncommon: Insomnia, anxiety, restlessness.

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

Nervous system disorders

Common: Fatigue or drowsiness, headache, dizziness, or sensation of unsteadiness.

Uncommon: Insomnia, excitement, irritability.

Rare: Paresthesia (numbness, tingling, "pins and needles" sensation, etc., more frequent in hands, feet, arms, or legs).

Very rare: Aseptic meningitis. In most reported cases of aseptic meningitis associated with ibuprofen, the patient had some form of autoimmune disease (such as systemic lupus erythematosus or other collagen diseases), which constituted a risk factor. Symptoms of aseptic meningitis observed included neck stiffness, headache, nausea, vomiting, fever, or disorientation.

Eye disorders

Uncommon: Visual disturbances.

Rare: Abnormal or blurred vision.

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

Ear and labyrinth disorders

Common: Vertigo.

Uncommon: Tinnitus (ringing or buzzing in the ears).

Rare: Hearing difficulty.

Cardiac disorders

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

Very rare: Palpitations, cardiac failure.

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

Vascular disorders

Edema (fluid retention), hypertension, and heart failure have also been observed in association with treatment with ibuprofen (arginine)-type medicines.

Very rare: Hypertension.

Frequency not known: Arterial thrombosis.

Respiratory disorders

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

Frequency not known: Throat irritation.

Gastrointestinal disorders

The most common adverse effects associated with medicines such as Difenadol rapid are gastrointestinal: peptic ulcers, gastrointestinal bleeding, perforations (in some cases fatal), especially in elderly patients.

Common: Gastrointestinal discomfort such as pyrosis (heartburn, reflux), abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, and minor gastrointestinal bleeding, which may exceptionally lead to anemia.

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

Rare: Vomiting blood.

Very rare: Inflammation of the esophagus, pancreatitis, intestinal stenosis.

Frequency not known: Anorexia.

Hepatobiliary disorders

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

Skin and subcutaneous tissue disorders

Common: Skin rash.

Uncommon: Skin redness, itching or swelling of the skin (angioedema, urticaria), purpura (purple spots on the skin).

Rare: Anaphylactic reaction.

Very rare: Medicines containing ibuprofen (arginine) may, very rarely, be associated with severe blistering reactions such as Stevens-Johnson syndrome (widespread erosions affecting the skin and two or more mucous membranes, and purplish lesions, primarily on the trunk) and toxic epidermal necrolysis (erosions of mucous membranes and painful lesions with necrosis and detachment of the epidermis). Hair loss, erythema multiforme (skin lesion). Rarely, severe skin infections and soft tissue complications may occur during chickenpox.

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

Renal and urinary disorders

Rare: Hematuria (presence of blood in urine).

Very rare: Edema (signs that may indicate kidney disease, which sometimes may include renal failure); kidney 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 renal failure cannot be excluded.

General disorders

Very rare: Worsening of inflammation during infectious processes.

Frequency not known: Edema.

Investigations

Rare: Abnormal liver function tests.

Frequency not known: Abnormal kidney function tests.

To date, no severe allergic reactions have been reported with Difenadol rapid, although they cannot be ruled out. Manifestations of such effects could include fever, skin rash, abdominal pain, severe 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 occur, stop treatment immediately and consult your doctor without delay:

• Allergic reactions such as skin rashes, facial swelling, wheezing, or difficulty breathing.
• Vomiting blood or material resembling coffee grounds.
• Blood in stools or bloody diarrhea.
• Severe stomach pain.
• Blisters or extensive 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.

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

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Difenadol rapid

Keep this medicine out of the 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 expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to properly dispose of containers and unused medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of Difenadol rapid

• The active substance 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 flavour (containing glucose in maltodextrin derived from maize and other excipients), and purified water.

Appearance of Difenadol rapid and contents of the pack

White granules with a characteristic orange odour.

Presented in packs containing 12 or 20 sealed paper/aluminium sachets.

Marketing Authorisation Holder and Manufacturer

LABORATORIOS NORMON, S.A.

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

Date of the most recent revision of this leaflet: January 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/