ESPIDIFEN 400 mg ORAL SOLUTION GRANULES, MINT FLAVOR

Pregnancy and Breastfeeding

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

Espidifen 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 or more difficult 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 medication, you should not drive or use hazardous machinery. If you only take one dose of Ibuprofen (Arginine) or take it for a short period, you do not need to take special precautions.

Espidifen Contains Aspartame, Sucrose, Butylated Hydroxyanisole (E 320), and Sodium

This medication contains 25 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 because the body is unable to eliminate it properly.

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

This medication contains 57 mg of sodium (the main component of table salt) in each sachet. This is equivalent to 2.85% of the maximum recommended daily sodium intake for an adult.

This medication may cause local reactions or irritation of mucous membranes because it contains butylated hydroxyanisole (E320).

3. How to take Espidifen

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

Your doctor will indicate the duration of treatment with Espidifen. Do not suspend treatment beforehand, as this will not achieve the expected results. Similarly, do not use this medication for longer than indicated by your doctor.

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).

This medication is administered orally.

Patients with stomach discomfort should take the medication with milk or during/after meals.

Adults and adolescents

In adults and adolescents from 12 to 18 years old, take one sachet (400 mg) every 6 to 8 hours, depending on the intensity of the condition and response to treatment.

In some cases, higher doses may be required, but in any case, it is recommended not to exceed the maximum daily dose of 2,400 mg in adults and 1,600 mg in adolescents from 12 to 18 years old.

Use in elderly patients

If you are over 60 years old, your doctor may prescribe a lower dose than usual. If so, the dose can only be increased once your doctor has checked that you tolerate the medication well.

Use in patients with kidney and/or liver disease

If you have kidney and/or liver disease, your doctor may prescribe a lower dose than usual. If so, take the exact dose prescribed by your doctor.

If you think the effect of Espidifen is too strong or too weak, inform your doctor or pharmacist.

Use in children

The use of this medication is not recommended 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.

If you take more Espidifen than you should

In case of overdose or accidental ingestion, consult a doctor or pharmacist immediately, go to the nearest hospital, or call the Toxicology Information Service (telephone: 91.5620420) indicating the medication and the amount ingested, to inform about the risk and ask for advice on the measures to be taken.

The symptoms of overdose may include nausea, stomach pain, vomiting (which may be bloody), gastrointestinal bleeding (see also section 4 below), diarrhea, headache, ringing in the ears, confusion, and tremulous eye movement. Agitation, drowsiness, disorientation, or coma may also occur. Occasionally, patients develop convulsions. At high doses, somnolence, chest pain, palpitations, loss of consciousness, convulsions (mainly in children), weakness, and dizziness, blood in the urine, low potassium levels in the blood, feeling of cold body, and respiratory problems have been reported. Additionally, the prothrombin time/INR may be prolonged, probably due to interference with the actions of circulating coagulation factors. Acute renal failure and liver damage may occur. An exacerbation of asthma in asthmatics is possible. Additionally, there may be low blood pressure and difficulty breathing.

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

If you forget to take Espidifen

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

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

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

4. Possible adverse effects

Like all medications, this medication can cause adverse effects, although not all people suffer from them.

Adverse effects of medications like Espidifen 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); 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 unknown (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 occur during treatment with ibuprofen, it is recommended to go to the doctor immediately, in case antibiotic therapy needs to be initiated.

Blood and lymphatic system disorders

Rare: Aplastic anemia (bone marrow failure 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 pale skin), decreased granulocytes (a type of white blood cell that can predispose to infections), pancytopenia (deficiency of red, white, and blood platelets), agranulocytosis (very significant decrease in granulocytes), hemolytic anemia (premature destruction of red blood cells). The first symptoms are: fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, extreme fatigue, nosebleeds, and skin bleeding. Prolongation of bleeding time.

Immune system disorders

Uncommon: 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

Uncommon: 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.

Uncommon: 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

Uncommon: Vision disturbances.

Rare: Abnormal or blurred vision.

Frequency unknown: Papilledema (inflammation of the optic nerve).

Ear and labyrinth disorders

Frequent: Vertigo.

Uncommon: Ringing or buzzing in the ears.

Rare: Hearing difficulty.

Cardiac disorders

Medications like Espidifen 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 unknown: Heart failure, 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 medications of the ibuprofen type (arginine).

Very rare: Arterial hypertension.

Frequency unknown: Arterial thrombosis.

Respiratory disorders

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

Frequency unknown: Throat irritation.

Gastrointestinal disorders

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

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

Uncommon: 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 unknown: 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.

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

Rare: Anaphylactic reaction.

Very rare: Medications like Espidifen 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 purple-colored lesions, 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 can occur during chickenpox.

Frequency unknown: Photosensitivity (skin reactions due to light influence), worsening of skin reactions. A severe skin reaction known as DRESS syndrome can 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 Espidifen if you present these symptoms and seek immediate medical attention. See also section 2.

Renal and urinary disorders

Rare: Hematuria (blood in the urine).

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

General disorders

Very rare: Worsening of inflammation during infectious processes.

Frequency unknown: Edema.

Investigations

Rare: Alteration of liver function tests.

Frequency unknown: Alteration of kidney function tests.

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

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

• Allergic reactions such as skin rashes, swelling of the face, wheezing in the chest, or difficulty breathing.
• Vomiting blood or coffee grounds-like vomit.
• Blood in the stool or bloody diarrhea.
• Severe stomach pain.
• Blisters 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.
• Vision disturbances.

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

• Reddish, non-raised, target-like, 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 can 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. The symptoms usually appear at the start of treatment (acute generalized exanthematous pustulosis).

Reporting 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 Medications: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Espidifen

Keep out of sight and reach of children.

No special storage conditions are required.

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

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need in the SIGRE point of your usual pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Espidifen

The active ingredient is ibuprofen. Each sachet contains 400 mg of ibuprofen (as 770 mg of ibuprofen arginine).

The other components (excipients) are: aspartame (E951), sucrose, sodium hydrogen carbonate, sodium saccharin, peppermint flavor, and anise flavor (contains butylhydroxyanisole (E 320)). See section 2. "Espidifen contains aspartame, sucrose, butylhydroxyanisole (E 320), and sodium".

Appearance of Espidifen and package contents

Oral solution granules, white in color.

Each package contains 30 sachets with granules.

Marketing authorization holder

Zambon, S.A.U.

Maresme, 5. Can Bernades-Subirà Industrial Estate

08130 Sta. Perpètua de Mogoda (Barcelona)

Spain

Manufacturer

Zambon, S.p.A.

Via della Chimica, 9

36100 Vicenza

Italy

or

Zambon, S.A.U.

Maresme, 5. Can Bernades-Subirà Industrial Estate

08130 Sta. Perpètua de Mogoda (Barcelona)

Spain

Date of the last revision of this prospectus:November 2024

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/