DIFENADOL 400 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Difenadol 400 mg Film-Coated Tablets

ibuprofen

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 or pharmacist.

• Keep this leaflet, 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 or pharmacist, even if they are not listed in this leaflet. See section 4.
• You should consult a doctor if it worsens or does not improve after 3 days if you have a fever or 4 days for pain treatment in case you are an adult. You should consult a doctor if it worsens or does not improve after 3 days in case you are an adolescent.

Contents of the Package Leaflet

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

1. What is Difenadol and what is it used for

Difenadol contains the active substance ibuprofen. Ibuprofen is a medicine that reduces fever and relieves pain (non-steroidal anti-inflammatory medicine (NSAID).

In adults and adolescents from 40 kg body weight (12 years and over) it is used for the short-term symptomatic treatment of mild to moderate pain and/or fever.

2. What you need to know before taking Difenadol

Do not take Difenadol

• If you are allergic (hypersensitive) to ibuprofen or any of the other ingredients of this medicine (listed in section 6). Reactions that indicate allergy could be: swelling of the eyelids, lips, tongue or throat.
• If you have ever had an allergic reaction (such as bronchospasm (tension of the lung muscles that can cause shortness of breath), asthma (nasal secretion, itching and inflammation of the nasal passages with sneezing), hives (a type of skin rash), or angioedema (swelling under the skin) after taking ibuprofen, acetylsalicylic acid or other similar analgesics (NSAIDs).
• If you have bleeding disorders or blood coagulation disorders.
• If you have an active ulcer or a history of recurrent stomach/duodenal ulcers (peptic ulcers) or bleeding (two or more episodes of proven ulceration or bleeding).
• If you have a history of gastrointestinal bleeding or perforation associated with previous treatment with NSAIDs.
• If you have had a stroke or other active bleeding.
• If you have severe liver, kidney, or 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

Adverse reactions are minimized by using the lowest effective dose for the shortest duration.

You should consult your treatment with your doctor or pharmacist before taking Difenadol:

• If you have systemic lupus erythematosus (SLE, sometimes known as lupus) or a connective tissue disease (autoimmune diseases that affect connective tissue).
• If you have or have had intestinal disease (ulcerative colitis or Crohn's disease) as your condition may worsen.
• If you have hereditary disorders of blood formation (e.g., acute intermittent porphyria).
• If you have reduced liver or kidney function.
• After undergoing major surgery.
• If you are sensitive (allergic) to other substances.
• If you have hay fever (allergy to pollen), nasal polyps, or chronic obstructive respiratory disorders, there is an increased risk of suffering allergic reactions. These allergic reactions can present as asthma attacks (called analgesic asthma). Quincke's edema or hives.
• Suffer from dehydration.
• If you have an infection; see the "Infections" heading later.

Effects on the gastrointestinal tract

The use of ibuprofen in combination with other non-steroidal anti-inflammatory medicines (NSAIDs), including so-called COX-2 inhibitors (cyclooxygenase-2 inhibitors), should be avoided.

Gastrointestinal bleeding, ulcers, and perforation:

There have been reports of gastrointestinal bleeding, ulcers, and perforation, (which can be fatal) during treatment with NSAIDs. At any time during treatment, with or without prior warning symptoms, and with or without a history of previous serious gastrointestinal events.

The risk of experiencing gastrointestinal bleeding, ulcers, and perforation is higher with increasing doses of NSAIDs and is higher in patients with a history of ulcers, especially with complications of bleeding or perforation (see section 2 "Do not take Difenadol") and in elderly patients. These patients should start treatment with the lowest available dose.

For these patients, as well as for patients who require additional treatment with low doses of acetylsalicylic acid or other medications that may increase the risk of gastrointestinal disorders, your doctor will consider the possibility of associating a stomach protective medication (e.g., misoprostol or proton pump inhibitors).

If you have a history of adverse reactions that affect the gastrointestinal tract - especially in elderly patients - consult your doctor in case of unusual abdominal symptoms (especially gastrointestinal bleeding), particularly at the start of therapy.

Cautious use is recommended if you are also taking other medications that may increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants (anticoagulants like warfarin), selective serotonin reuptake inhibitors (used to treat psychiatric disorders, including depression), or platelet aggregation inhibitors like acetylsalicylic acid (see section 2 "Other medicines and Difenadol").

You should stop treatment and consult a doctor if you develop gastrointestinal bleeding or ulcers during treatment with Difenadol.

Effects on the cardiovascular system

Anti-inflammatory/analgesic medicines like ibuprofen 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.

You should discuss your treatment with your doctor or pharmacist before taking ibuprofen 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 if you are a smoker.

Severe skin reactions (SCARs)

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), acute generalized exanthematous pustulosis (AGEP), in association with ibuprofen treatment. Discontinue treatment with Difenadol and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

If you have chickenpox, it is advisable to avoid the use of ibuprofen.

Infections

Difenadol may mask the signs of an infection, such as fever and pain. Consequently, Difenadol may delay 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.

Other warnings

In very rare cases, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. At the first signs of a hypersensitivity reaction after taking ibuprofen, treatment should be discontinued and a doctor consulted. Medically required measures, in line with the symptoms, should be initiated by specialized personnel.

Ibuprofen may reversibly inhibit platelet aggregation and function (platelet aggregation). Therefore, patients with coagulation disorders should be carefully monitored.

During prolonged use of ibuprofen, regular monitoring of liver function tests, kidney function, and blood counts is required.

Prolonged use of any type of pain reliever for headache may worsen it. If this situation is observed or suspected, a doctor should be consulted and treatment discontinued.

In general, the habitual use of different types of pain relievers can lead to the appearance of serious kidney problems with a risk of kidney failure (analgesic nephropathy). This risk can be increased in conditions of physical exertion associated with loss of salts and dehydration. Therefore, it should be avoided.

The risk of kidney failure increases in dehydrated patients, elderly patients, and those taking diuretics and ACE inhibitors.

In case of vision problems, please consult your doctor.

Signs of an allergic reaction to this medicine, including breathing problems, swelling of the face and neck area (angioedema), and chest pain, have been reported with ibuprofen. Discontinue treatment with ibuprofene immediately and contact your doctor or the emergency medical service as soon as possible if you observe any of these signs.

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 (see also the warning about bleeding at the beginning of section 2).

Adolescents

There is a risk of kidney failure in dehydrated adolescents.

Other medicines and Difenadol

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

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

• Digoxin, phenytoin, and lithium: the combined use of ibuprofen and digoxin (used for heart failure), phenytoin (used to treat seizures/epilepsy), or lithium (used to treat, for example, depression) may increase the concentration of these medicines in the blood. Monitoring of lithium serum levels is necessary. Generally, monitoring of digoxin and phenytoin serum levels is not required when used as indicated (3 or 4 days at most).
• Anticoagulants (to thin the blood/prevent blood clots, e.g., acetylsalicylic acid, warfarin, ticlopidine). NSAIDs may increase the effects of anticoagulants like warfarin.
• Diuretics and blood pressure medications:

Difenadol may reduce the effect of medicines used to increase urine production (diuretics) and lower blood pressure (antihypertensive medicines, e.g., ACE inhibitors, beta-blockers, and angiotensin II receptor antagonists). The combined administration of ibuprofen and potassium-sparing diuretics (medicines used to increase urine elimination) may lead to an increase in potassium levels in the blood.

• Blood pressure-lowering medicines (ACE inhibitors like captopril, beta-blockers like atenolol, and angiotensin II receptor antagonists like losartan): ibuprofen may reduce the effect of ACE inhibitors (used to treat heart failure and high blood pressure). Additionally, during combined use, there is a higher risk that kidney dysfunction may occur.
• Colestyramine (a medicine used to reduce cholesterol) in combination with ibuprofen may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical importance is unknown.
• Other analgesics: the combined use of ibuprofen with other anti-inflammatory and analgesic medicines of the NSAID group, including COX-2 inhibitors (e.g., celecoxib), may increase the risk of gastrointestinal ulcers and bleeding.
• Platelet aggregation inhibitors and certain antidepressants (selective serotonin reuptake inhibitors/SSRIs) may increase the risk of gastrointestinal bleeding.
• Methotrexate: the administration of ibuprofen within 24 hours before or after the administration of methotrexate (used to treat certain types of cancer and rheumatism) may cause an increase in methotrexate concentrations and an increase in its side effects.
• Ciclosporin and tacrolimus: there is a higher risk that immunosuppressive medicines like ciclosporin and tacrolimus may damage the kidneys.
• Probenecid or sulfinpyrazone: medicines containing probenecid or sulfinpyrazone (used in patients with gout) may delay the excretion of ibuprofen. This may cause ibuprofen to accumulate in the body, with an increase in its side effects.
• Sulfonylureas: during the combined use of ibuprofen and sulfonylureas (medicines used to treat diabetes), it is recommended to monitor blood sugar levels.
• Zidovudine: there is evidence suggesting a higher risk of hemarthrosis (accumulation of blood in the joints) and bruising (hematomas) in HIV-positive hemophilic patients who use zidovudine (a medicine against the AIDS virus) along with ibuprofen.
• Quinolone antibiotics: the risk of seizures (attacks) may increase when taking quinolone antibiotics, such as ciprofloxacin, and ibuprofen at the same time.
• Aminoglycosides: the combined use of ibuprofen with aminoglycosides (a type of antibiotic) with NSAIDs may decrease the elimination of aminoglycosides.
• Voriconazole and fluconazole (CYP2C9 inhibitors) used for fungal infections, as the effect of ibuprofen may increase. The dose of ibuprofen should be considered for reduction, particularly when a high dose of ibuprofen is administered with voriconazole or fluconazole.
• Ginkgo biloba (a herbal medicine) may increase the risk of bleeding with NSAIDs.
• Mifepristone: the combined use of mifepristone with other anti-inflammatory and analgesic medicines of the NSAID group (i.e., ibuprofen) may decrease the effect of mifepristone.
• Ritonavir: combined use with ritonavir (an antiviral medicine used to treat HIV infections) may increase the plasma concentrations of NSAIDs.
• Alcohol, bisphosphonates, and oxpentifylline (pentoxifylline): the combined use of ibuprofen with alcohol, bisphosphonates (used for osteoporosis), or pentoxifylline (for treating peripheral arterial circulatory problems) may increase gastrointestinal side effects and the risk of bleeding and ulcers.
• Baclofen (a muscle relaxant) due to the high toxicity of baclofen.
• Medicines for treating inflammation (corticosteroids) due to the increased risk of gastrointestinal ulcers or bleeding.

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

Taking Difenadol with alcohol

The adverse reactions of ibuprofen may be increased with the consumption of alcohol, especially those affecting the central nervous system and the gastrointestinal tract. You should not drink alcohol while taking ibuprofen.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

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 for your fetus. It may affect your and your baby's tendency to bleed and delay or prolong labor more than expected.

Do not take this medicine during the first 6 months of pregnancy unless 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, if you take this medicine for more than a few days, it may cause kidney problems for your fetus, which may lead to low levels of the fluid surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby's heart. If you need treatment during a period longer than a few days, your doctor may recommend additional checks.

Breastfeeding

Small amounts of ibuprofen pass into breast milk. However, as no harmful effects have been reported in children to date, it is not usually necessary to interrupt breastfeeding during short-term use of ibuprofen at the recommended dose for fever and pain.

Fertility

This product belongs to the group of NSAIDs that may affect fertility in women. This effect is reversible upon discontinuation of the medication. You should consult your doctor if you plan to become pregnant or if you have difficulty becoming pregnant.

Driving and using machines

Ibuprofen generally has a negligible influence on the ability to drive and use machines. However, at higher doses, adverse effects such as fatigue and dizziness may occur, and the ability to react may be affected while driving and operating machines. This is especially important when the medicine is combined with alcohol.

Difenadol contains sodium

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

3. How to take Difenadol

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

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 usual dose is:

Adults and adolescents from 40 kg in weight (from 12 years or older)

One tablet (400 mg) as a single dose.

The dosing interval should be chosen according to the observed symptoms and the recommended maximum daily dose. The interval between doses should not be less than 6 hours. Do not take more than 3 tablets (1200 mg) of ibuprofen in a 24-hour period.

This medication is not recommended for use in adolescents under 40 kg in weight or children under 12 years of age.

Adverse reactions can be minimized by using the lowest effective dose for the shortest possible time to control symptoms.

If you have severe liver or kidney disease or are an elderly patient, your doctor will indicate the correct dose to take, which will be the lowest possible dose.

Method of administration

Oral route.

Take the tablet with a glass of water.

Ibuprofen tablets should be swallowed whole, without chewing, crushing, or sucking to avoid discomfort in the mouth or throat irritation.

It is recommended that patients with sensitive stomachs take ibuprofen with food. Difenadol is intended for short-term use only.

For adults

If you need this medication for more than 3 days to treat fever or for more than 4 days to treat pain, or if symptoms worsen, you should consult a doctor.

For adolescents

If adolescents need this medication for more than 3 days, or if symptoms worsen, they should consult a doctor.

If you take more Difenadol than you should

If you have taken more ibuprofen than you should, or if a child has accidentally ingested the medication, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication 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, headache, ringing in the ears, confusion, and involuntary eye movements.

Additionally, it could cause blurred vision and worsening of asthma in asthmatics.

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

At high doses, symptoms of drowsiness, excitement, disorientation, chest pain, palpitations, loss of consciousness, seizures (mainly in children), weakness, and dizziness, blood in the urine, low potassium levels in the blood, low blood pressure, increased prothrombin time/INR, probably due to interference with the action of circulating coagulation factors, acute kidney failure, liver damage, respiratory failure, cyanosis, decreased body temperature, respiratory problems with decreased breathing, and chills have been reported.

If you forget to take Difenadol

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

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone gets them.

The most common side effects observed affect the digestive tract. Stomach/duodenal ulcers (peptic ulcers), perforation, or bleeding may occur, sometimes fatally, especially in elderly patients (see section 2: "Warnings and precautions"). Nausea, vomiting, diarrhea, flatulence, constipation, digestive problems, abdominal pain, blood in stools, vomiting blood, and ulcers (stomatitis) in the mouth and throat area may occur. Exacerbation of colitis and Crohn's disease (see section 2: "Warnings and precautions") has been reported after its use. Gastritis has been observed less frequently. In particular, the risk of developing gastrointestinal bleeding depends on the dose level and treatment duration.

Edema (swelling), high blood pressure, and heart failure have been observed in association with NSAID treatments.

More serious side effects

• Stop treatment with ibuprofen and seek immediate medical attention if you notice the following symptoms:

• Red, non-raised, target-like, or circular patches on the torso, often with blisters in the center, skin peeling, mouth ulcers, throat ulcers, nose ulcers, genital ulcers, and eye ulcers. These severe skin rashes can be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].
• Widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome).
• Widespread, 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).

• Stop treatment and go to your doctor immediately if you develop severe allergic reactions (hypersensitivity), a very rare side effect (may affect up to 1 in 10,000 people):

These may manifest as:

• Facial swelling (facial edema), tongue, or throat swelling (laryngeal edema with constriction of the airways).
• Difficulty breathing.
• Rapid heartbeat.
• Drop in blood pressure to fatal shock.

• You should consult your doctor immediately if you experience an infection with symptoms such as fever and severe deterioration of your general condition, or fever with symptoms of local infection, such as sore throat/pharynx/mouth or urinary problems. Ibuprofen may cause a decrease in white blood cells [agranulocytosis, a very rare side effect (may affect up to 1 in 10,000 people)] with a decrease in resistance to infection. You should consult your doctor immediately if you experience an infection with symptoms such as fever and severe deterioration of your general condition, or fever with symptoms of local infection, such as sore throat/pharynx/mouth or urinary problems. It is essential to inform your doctor about your medication.

• Severe blistering reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome), and/or erythema multiforme [a very rare side effect (may affect up to 1 in 10,000 people)]. A severe skin reaction known as DRESS syndrome (by its English acronym) may occur. The symptoms of DRESS syndrome include: skin rash, fever, swollen lymph nodes, and elevated eosinophils (a type of white blood cell) [frequency not known (frequency cannot be estimated from available data)]. Stop taking ibuprofen and contact a doctor if you develop a skin rash or lesions on the mucous membranes. Severe rashes may include blisters on the skin, especially on the legs, arms, hands, and feet, and may include the face and lips. A more severe skin reaction, toxic epidermal necrolysis (erosions on mucous membranes and painful lesions with necrosis and shedding of the epidermis), may occur.

• Stop taking ibuprofen if you experience relatively severe pain in the upper abdomen, vomit blood, have black stools, or bloody diarrhea, and inform your doctor immediately.

• If you have edema (fluid retention), especially in patients with high blood pressure or kidney problems, nephrotic syndrome, interstitial nephritis (kidney disorder) that may be associated with acute kidney failure (renal failure) [very rare side effects (may affect up to 1 in 10,000 people)]. Decreased urine production, swelling caused by fluid accumulation in tissues (edema), and discomfort (generally feeling unwell) may be signs of kidney failure.

If you have any of these side effects or if they worsen, stop treatment and go to your doctor immediately.

Other side effects

Frequent (may affect more than 1 in 10 people)

• Gastrointestinal disorders, stomach acid, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation, digestive problems, and mild gastrointestinal bleeding, which may cause anemia in exceptional cases.

Uncommon (may affect up to 1 in 100 people)

• Central nervous system disorders, such as headache, dizziness, insomnia, agitation, irritability, or fatigue.
• Visual disturbances. In this case, you should discontinue treatment with ibuprofen and consult your doctor.
• Especially in elderly patients, gastrointestinal ulcers, sometimes with bleeding and perforation (hole in the intestinal walls), stomatitis (inflammation of the mouth mucosa), gastritis (inflammation of the stomach), worsening of colitis and Crohn's disease, which can be fatal.
• Gastritis (inflammation of the stomach).
• Hypersensitivity reactions such as skin rash and itching, as well as asthma attacks (with possible drop in blood pressure).

Stop taking ibuprofen and inform your doctor immediately.

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

• Tinnitus (ringing in the ears).
• Hearing loss.
• Kidney damage (papillary necrosis), high uric acid levels in the blood, high urea levels in the blood.

Very rare (may affect up to 1 in 10,000 people)

• Disorders of blood cell formation, such as decreased red blood cells or hemoglobin (anemia), white blood cells (leukopenia), or platelet levels (thrombocytopenia); and other blood disorders (pancytopenia, agranulocytosis, eosinophilia, coagulopathy, neutropenia, aplastic anemia, or hemolytic anemia). The first symptoms are: fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, extreme fatigue, nosebleeds, and skin bleeding.
• Worsening of inflammation associated with infection (e.g., necrotizing fasciitis) related to the use of certain analgesics (NSAIDs) has been described. If symptoms of an infection or worsening of an infection (e.g., redness, swelling, heat, pain, fever) appear during the administration of ibuprofen, you should consult your doctor immediately. It will be determined if anti-infective/antibiotic therapy is indicated.
• Symptoms of aseptic meningitis (inflammation of the brain and its lining not caused by infection) have been observed during ibuprofen intake, such as acute headache, nausea, vomiting, fever, neck stiffness, or transient loss of consciousness with the use of ibuprofen. Patients with autoimmune disorders (LES, mixed connective tissue disease) seem to be predisposed.
• Low blood sugar levels (hypoglycemia).
• Low sodium levels in the blood (hyponatremia).
• Palpitations, heart failure, heart attack.
• High blood pressure (hypertension).
• Vasculitis (inflammation of blood vessels).
• Inflammation of the esophagus or pancreas (pancreatitis), narrowing of the large or small intestine (intestinal stenosis).
• Psychotic reactions, hallucinations, confusion, depression, and anxiety.
• Asthma, difficulty breathing (dyspnea), bronchospasm.
• Yellowing of the eyes and/or skin (jaundice), liver dysfunction, liver damage, especially with prolonged treatment, liver failure, acute hepatitis.
• Severe skin reactions such as rash with redness and blisters (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis/Lyell syndrome), hair loss (alopecia), purple or red discoloration of the skin (purpura), or photosensitivity reactions (triggered by sunlight).
• Severe skin infections and soft tissue complications may exceptionally occur during chickenpox.

Frequency not known (cannot be estimated from available data)

• Nasal mucosa inflammation (rhinitis).
• Numbness and tingling sensation (paresthesia) and optic nerve inflammation (optic neuritis).
• Sudden loss of kidney function.
• Generalized red scaly rash with bumps under the skin and blisters, mainly located on skin folds, torso, and upper limbs, accompanied by fever at the start of treatment (acute generalized exanthematous pustulosis). Stop taking this medication if you experience these symptoms and seek medical attention immediately. See also section 2.
• Chest pain, which may be a sign of a potentially severe allergic reaction called Kounis syndrome.

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

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Medicines and Health Products Agency's (AEMPS) website: www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Difenadol

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the box after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and unused medications at the pharmacy's SIGRE point. If in doubt, ask your pharmacist how to dispose of the packaging and unused medications. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Difenadol

The active ingredient is ibuprofen. Each tablet contains 400 mg of ibuprofen.

The other ingredients are:

Core of the tablet:microcrystalline cellulose, calcium phosphate, sodium croscarmellose, hypromellose, povidone, stearic acid, talc.

Coating:hypromellose, titanium dioxide (E-171), macrogol, and talc.

Appearance of the product and package contents

White or almost white film-coated tablets, oblong, and biconvex, engraved with "I400" on one side and smooth on the other, with a diameter of 14.4 mm x 7.2 mm ± 10%.

Each package contains 12 or 20 film-coated tablets in aluminum-PVC blisters.

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 leaflet:January 2025

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