IBUPROFEN (ARGININE) COMBIX 600 mg ORAL SOLUTION GRANULES

Introduction

PROSPECTUS: INFORMATION FOR THE USER

Ibuprofen (arginine) Combix 600 mg granulate for oral solution EFG

Read the entire prospectus carefully before starting to take the medication.

• Keep this prospectus as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed to you personally and should not be given to others, even if they have the same symptoms, as it may harm them.
• If you consider that any of the adverse effects you suffer is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist. See section 4.

Contents of the prospectus:

1. What is Ibuprofen (arginine) Combix and what is it used for
2. Before taking Ibuprofeno (arginina) Combix
3. How to take Ibuprofeno (arginina) Combix
4. Possible adverse effects
5. Storage of Ibuprofeno (arginina) Combix
6. Additional information

1. What is Ibuprofen (arginine) Combix and what is it used for

Ibuprofen (arginine) belongs to the group of medications called non-steroidal anti-inflammatory drugs (NSAIDs).

This medication is indicated for the treatment of pain: headaches, toothaches, post-operative pain, menstrual pain, symptomatic treatment of headache and febrile states. Ibuprofen (Arginine) is also indicated in rheumatoid arthritis (including juvenile rheumatoid arthritis), ankylosing spondylitis, osteoarthritis, and other acute or chronic rheumatic processes, as well as in other muscle (sprains and strains) and bone conditions where pain and inflammation occur.

2. Before taking Ibuprofen (arginine) Combix

Do not take Ibuprofen (arginine) Combix

• If you are allergic to Ibuprofen or other medications such as acetylsalicylic acid or other non-steroidal anti-inflammatory drugs. Such reactions could be: skin rash with itching, swelling of the face, lips, or tongue, nasal discharge, difficulty breathing, or asthma.
• If you have had a stomach or duodenal ulcer or have suffered a perforation of the digestive tract.
• If you have severe heart failure.
• If you are in the third trimester of pregnancy.
• If you have a severe liver or kidney disease.

Warnings and precautions:

Be especially careful with Ibuprofen (arginine) Combix:

• 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 greater when high doses and prolonged treatments are used, in patients with a history of peptic ulcer and in the elderly. In these cases, your doctor will consider the possibility of associating a stomach-protecting medication.

• If you take medications that alter blood coagulation, such as oral anticoagulants, antiplatelet agents of the type of acetylsalicylic acid. 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 or ulcerative colitis, as medications of the type of Ibuprofen (arginine) Combix 600 mg may worsen these conditions.
• If you have had kidney or liver disease.
• If you have edema (fluid retention).

• If you have asthma or any other respiratory disorder.
• If you have heart disease, kidney or liver disease, are over 60 years old, or need to take the medication 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.
• See the "Infections" section below.

Infections: Ibuprofen (arginine) Combix may hide the signs of an infection, such as fever and pain. Therefore, Ibuprofen (arginine) Combix 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 medication while having an infection and the symptoms of the infection persist or worsen, consult a doctor without delay, as this is an important sign of infection.

With ibuprofen, signs of allergic reaction to this medication have been reported, such as respiratory problems, swelling of the face and neck area (angioedema), and chest pain. Stop using Ibuprofen (arginine) Combix immediately and contact your doctor or the medical emergency service immediately if you notice any of these signs.

Severe skin reactions have been reported, such as 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 Ibuprofen (arginine) Combix and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Cardiovascular precautions

Anti-inflammatory/analgesic medications like ibuprofen may be associated with a small increased risk of suffering a 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 Ibuprofen (arginine) Combix 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, this type of medication may produce fluid retention, especially in patients with heart failure and/or high blood pressure (hypertension).

Skin reactions

Severe skin reactions have been reported in association with Ibuprofen (arginine) Combix treatment. Stop taking Ibuprofen (arginine) Combix and consult a doctor immediately if you present any skin rash, lesions on the mucous membranes, blisters, or other signs of allergy, as these may be the first signs of a severe skin reaction. See section 4.

Use of Ibuprofen (arginine) Combix with other medications:

Inform your doctor or pharmacist if you are using or have recently used any other medication, even those purchased without a prescription, as it may be necessary to discontinue treatment or adjust the dose of one of them.

Ibuprofen (arginine) Combix may affect or be affected by other medications. For example:

• Other non-steroidal anti-inflammatory drugs.

• Anticoagulant medications (e.g., to treat coagulation problems/prevent coagulation, e.g., acetylsalicylic acid, warfarin, ticlopidine).

• Lithium (medication used to treat depression). Your doctor may adjust the dose of this medication.
• Methotrexate. Your doctor may adjust the dose of this antimetabolite medication (slows down the growth of certain cells produced by the body).
• Mifepristone (abortion inducer).
• 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.
• Diuretics (medications used to increase urine elimination).
• Fluconazole (for the treatment of fungal infections).
• 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 (for diabetes).
• Tacrolimus (used in organ transplants to prevent rejection).
• Zidovudine (medication against the AIDS virus).
• Medications that lower high blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, and angiotensin-II receptor antagonists such as losartan).

Other medications may also affect or be affected by treatment with Ibuprofen (arginine) Combix. Therefore, you should always consult your doctor or pharmacist before using Ibuprofen (arginine) Combix with other medications.

Taking Ibuprofen (arginine) Combix with food and beverages:

You can take it alone or with food. In general, it is recommended to take it before meals to reduce the possibility of stomach discomfort.

Pregnancy and lactation

Precautions during pregnancy and in women of childbearing age

Since the administration of medications of the type of Ibuprofen (arginine) Combix has been associated with an increased risk of congenital anomalies/abortions, it is not recommended to administer it during the first and second trimester of pregnancy unless it is strictly necessary and your doctor recommends it. In these cases, the dose and duration will be limited to the minimum possible. From the 20th week of pregnancy, Ibuprofen (arginine) Combix may cause kidney problems in the fetus if taken for more than a few days, which may cause 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 period longer than a few days, your doctor may recommend additional checks.

In the third trimester, the administration of Ibuprofen (arginine) Combix is contraindicated. It may cause kidney and heart problems in the fetus. It may affect you and your baby's tendency to bleed and delay or prolong labor more than expected.

For women of childbearing age, it should be taken into account that medications of the type of Ibuprofen (arginine) Combix have been associated with a decrease in fertility.

Breastfeeding:

Although only small amounts of the medication pass into breast milk, it is recommended not to take ibuprofen for prolonged periods during breastfeeding.

Therefore, if you become pregnant or are breastfeeding, consult your doctor or pharmacist before using any medication.

Use in children

Do not administer to children under 14 years old.

Driving and using machines:

Although this effect is rare, this medication should be used with caution in patients whose activity requires attention and who have observed drowsiness, dizziness, or depression during treatment.

Important information about some of the components of Ibuprofen (arginine) Combix:

This medication may be harmful to people with phenylketonuria because it contains aspartame, which is a source of phenylalanine.

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

3. How to take Ibuprofen (arginine) Combix

Ibuprofen (arginine) Combix is administered orally.

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

The recommended average dosage is 1 sachet of Ibuprofen (arginine) Combix every 12 hours. If stomach discomfort is detected after taking the medication, it should be administered together with milk or during meals. In rheumatoid arthritis, higher doses may be required, but in any case, it is recommended not to exceed the daily dose of 2,400 mg of ibuprofen (4 sachets), taking into account that the effective lowest dose should be administered.

In elderly patients, the dosage should be established by the doctor, as it may be necessary to reduce the usual dose. In case of kidney disorders, the doses should be adjusted since the medication is eliminated mainly through this route.

The use of this medication is not recommended in children under 14 years old, as the dose of ibuprofen it contains is not suitable for the recommended dosage in these children.

If you take more Ibuprofen (arginine) Combix than you should:

If you have taken more Ibuprofen (arginine) Combix than you should, or if a child has accidentally ingested the medication, consult a doctor or go to the nearest hospital immediately to find out about the risk and ask for advice on the measures to be taken.

If a severe overdose has occurred, the doctor will take the necessary measures.

In case of overdose or accidental ingestion, you can also call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

The symptoms of overdose may include nausea, stomach pain, vomiting (which may contain blood), headache, ringing in the ears, confusion, and involuntary eye movement. At high doses, symptoms such as drowsiness, chest pain, palpitations, loss of consciousness, convulsions (mainly in children), weakness, and dizziness, blood in the urine, low potassium levels in the blood, chills, and breathing problems have been reported.

If you forget to take Ibuprofen (arginine) Combix:

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

4. Possible Adverse Effects

Like all medications, Ibuprofen (arginine) Combix can produce adverse effects.

The observed adverse effects are described below according to their frequency of presentation:

Very frequent (at least 1 in 10 patients); Frequent (at least 1 in 100 patients); Infrequent (at least 1 in 1000 patients); Rare (at least 1 in 10,000 patients); Very rare (less than 1 in 10,000 patients).

The following adverse effects have been observed:

Gastrointestinal:

The most frequent adverse effects that occur with medications like Ibuprofen (arginine) Combix 600 mg are gastrointestinal: peptic ulcers, digestive bleeding, perforations (in some cases fatal), especially in the elderly. Nausea, vomiting, diarrhea, flatulence, constipation, heartburn, abdominal pain, blood in stool, oral thrush, worsening of ulcerative colitis, and Crohn's disease have also been observed. Gastritis has been observed less frequently.

Skin and allergic reactions:

Frequent:skin rash.

Infrequent:skin redness, itching or swelling of the skin, swelling of the lips, face, or tongue, increased nasal secretion, and difficulty breathing.

Rare:severe allergic reactions (anaphylactic shock).

Very rare:intense itching of the skin with sudden onset or blisters on the skin, joint pain, and fever (systemic lupus erythematosus), hair loss, skin reactions due to light influence.

Medications like Ibuprofen (arginine) Combix 600 mg may be associated, in very rare cases, with severe blistering reactions such as Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and allergic vasculitis.

Aseptic meningitis (inflammation of the membranes covering the brain and spinal cord), in most cases in patients with some autoimmune disease such as systemic lupus erythematosus.

Severe allergic reaction that can manifest with nausea, vomiting, swelling of the face, tongue, and throat, difficulty breathing, asthma, palpitations, hypotension, or shock.

Frequency not known: 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), the skin becomes sensitive to light. Stop taking Ibuprofen (arginine) Combix if you experience these symptoms and seek medical attention immediately. See also section 2.

Central Nervous System:

Frequent:headache, feeling of instability, and nervousness.

Infrequent:fatigue or drowsiness, insomnia, anxiety, vision changes, ringing or buzzing in the ears.

Rare:disorientation or confusion, depression, abnormal or blurred vision, and hearing difficulty.

Very rare:aseptic meningitis.

Blood:

Very rare:prolonged bleeding time, alterations in blood cells (the first symptoms may be: fever, sore throat, mouth ulcers, flu-like symptoms, excessive fatigue, nasal and skin bleeding).

Cardiovascular:

Medications like Ibuprofen (arginine) Combix may be associated with a moderate increase in the risk of suffering a heart attack ("myocardial infarction") or stroke.

Edema (fluid retention), hypertension, and heart failure have also been observed in association with treatments with medications of the type Ibuprofen (arginine) Combix.

Chest pain, which can be a sign of a potentially severe allergic reaction called Kounis syndrome.

Kidney:

Kidney disease.

Liver:

Rare:hepatitis (inflammation of the liver) and jaundice (yellowing of the skin). Medications like Ibuprofen (arginine) Combix may be associated, in rare cases, with liver damage.

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).

If you consider that any of the adverse effects you are experiencing is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

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

• Red, non-elevated, 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 hypertrophic lymph nodes (DRESS syndrome).
• Generalized, red, and scaly rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the start of treatment (acute generalized exanthematous pustulosis).

Adverse Effect Reporting

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 Ibuprofen (arginine) Combix

Keep Ibuprofen (arginine) Combix out of the reach and sight of children.

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

Expiration Date:

This medication should not be used after the expiration date indicated on the packaging. 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 at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Additional Information

Composition of Ibuprofen (arginine) Combix 600 mg granules for oral solution

The active ingredient is Ibuprofen. Each sachet contains 600 mg of Ibuprofen.

The other components (excipients) are: Arginine, Aspartame (E-951), Compression sugar (sucrose), sodium bicarbonate, sodium saccharin, sodium lauryl sulfate, menthol flavor (10.86.4580), mint flavor (506041 TP0504) contains gluten-free cornstarch, purified water.

Appearance of the product and packaging content

Sachets with granules for oral solution. It is presented in the form of white granules with a characteristic mint smell.

It is presented in packaging with 20 or 40 sachets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Laboratorio Farmacéutico Biocentury. Ctra. N-II, Km. 714 17242 Quart (Girona) Spain

or

Lamp S. Prospero S.p.A., Via de la Pace, 25 – 41030 San Prospero (MO). Italy

or

Toll Manufacturing Services S.L., C/Aragoneses, 2. 28108 Alcobendas (Madrid) 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/