IBUPROFENO PHARMA COMBIX 400 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Ibuprofeno Pharma Combix 400 mg Film-Coated Tablets EFG

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

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Ibuprofeno Pharma Combix and what is it used for

Ibuprofen belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs).

This medicine is used for the treatment of fever, treatment of pain of mild to moderate intensity including migraine, treatment of arthritis (inflammation of the joints, including usually those of the hands and feet, leading to swelling and pain), juvenile rheumatoid arthritis, osteoarthritis (a chronic disorder that causes damage to the cartilage), ankylosing spondylitis (inflammation that affects the joints of the spine), non-rheumatic inflammation, and primary dysmenorrhea (painful menstruation).

2. What you need to know before you take Ibuprofeno Pharma Combix

Do not take Ibuprofeno Pharma Combix

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take ibuprofen

• if you have edema (fluid retention),
• if you have or have had any heart disorder or have high blood pressure,
• if you have asthma or any other respiratory disorder,
• if you are already taking ibuprofen, inform your doctor as it may mask fever, which is an important sign of infection, making diagnosis difficult,
• if you have kidney or liver disease, are over 60 years old, or need to take the medicine for a prolonged period (more than 1 to 2 weeks), your doctor may need to perform regular checks. Your doctor will indicate the frequency of these checks,
• if you 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 elderly patients. In these cases, your doctor will consider the possibility of associating a stomach protective medication.

• if you are taking medications that alter blood coagulation, such as oral anticoagulants, antiplatelet agents of the acetylsalicylic acid type. You should also discuss the use of other medications that may increase the risk of such bleeding, such as corticosteroids and selective serotonin reuptake inhibitor antidepressants,
• if you have Crohn's disease (a chronic disease in which the immune system attacks the intestine, causing inflammation that usually produces bloody diarrhea) or ulcerative colitis, as ibuprofen-like medications can worsen these conditions,
• if you are being treated with diuretics (medicines used to increase urine production), as your doctor should monitor your kidney function,
• if you have systemic lupus erythematosus (a chronic disease that affects the immune system and can affect various vital organs, the nervous system, blood vessels, skin, and joints), as it may cause aseptic meningitis (inflammation of the meninges that protect the brain and spinal cord, not caused by bacteria),
• if you have acute intermittent porphyria (a metabolic disease that affects your blood and can cause symptoms such as reddish urine color, blood in urine, or liver disease), so that your doctor can assess the convenience or not of treatment with ibuprofen,
• if you suffer from headaches after prolonged treatment, do not take higher doses of the medication,
• if you have an infection: see the "Infections" section below.

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 immediately and contact your doctor or the emergency medical service immediately if you observe any of these signs.

Your doctor will perform stricter monitoring if you receive ibuprofen after undergoing major surgery.

It is advisable not to take this medication if you have chickenpox.

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

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.

Skin reactions

Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), have been reported in association with ibuprofen treatment. Discontinue ibuprofen treatment 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 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 this medication 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 can cause fluid retention, especially in patients with heart failure and/or high blood pressure (hypertension).

Respiratory disorders

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

Precautions during pregnancy and in women of childbearing age

Because the administration of ibuprofen-like medications 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. In these cases, the dose and duration will be limited to the minimum possible. It is believed that the risk increases with the dose and duration of treatment.

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

For women of childbearing age, it should be taken into account that ibuprofen-like medications have been associated with a decrease in fertility.

Infections

Ibuprofen may mask the signs of an infection, such as fever and pain. Consequently, ibuprofen may delay appropriate treatment of the infection, which can 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 your doctor without delay.

Other medications and Ibuprofeno Pharma Combix

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medications.

Ibuprofen may affect or be affected by other medications. For example:

• Other non-steroidal anti-inflammatory drugs, such as aspirin, as the risk of ulcer and gastrointestinal bleeding may increase.
• Antiplatelet agents (prevent the formation of thrombi or clots in blood vessels) such as ticlopidine.
• Anticoagulant medications (e.g., to treat coagulation problems/prevent coagulation, e.g., acetylsalicylic acid, warfarin, ticlopidine).
• Colestyramine (a medication used to treat high cholesterol).
• Selective serotonin reuptake inhibitors (used in depression).
• Lithium (a medication used to treat depression). Your doctor may adjust the dose of this medication.
• Methotrexate (for cancer and inflammatory diseases). Your doctor may adjust the dose of this medication.
• 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 production), as they may increase the risk of kidney toxicity.
• Pentoxifylline (for intermittent claudication).
• Probenecid (used in patients with gout or with penicillin in infections).
• Quinolone antibiotics such as norfloxacin.
• Sulfinpyrazone (for gout).
• Sulfonylureas such as tolbutamide (for diabetes), as they may cause hypoglycemia.
• Tacrolimus or cyclosporin (used in organ transplants to prevent rejection).
• Zidovudine (a 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).
• Thrombolytics (medications that dissolve clots).
• Aminoglycoside antibiotics such as neomycin.
• Ginkgo biloba tree extracts.
• CYP2C9 inhibitors (responsible for the metabolism of numerous drugs in the liver), such as voriconazole and fluconazole (used to treat fungal infections).

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

Taking ibuprofen may alter the following laboratory tests:

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

Tell your doctor if you are going to undergo a clinical analysis and are taking or have recently taken ibuprofen.

Taking Ibuprofeno Pharma Combix with food, drinks, and alcohol

It is recommended to take ibuprofen with milk or with food, or immediately after eating, to reduce the possibility of stomach discomfort. Do not drink alcohol as it may increase gastrointestinal adverse reactions.

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.

The use of this medication is not recommended in women who are trying to become pregnant.

Do not take ibuprofen during pregnancy, especially during the third trimester (see section precautions during pregnancy and in women of childbearing age), as it may harm the fetus or cause problems during delivery. It may cause kidney and heart problems in your fetus. It may affect your and your baby's tendency to bleed and delay or prolong labor more than expected. Do not take ibuprofen during the first 6 months of pregnancy unless it is absolutely necessary and your doctor advises you to do so. If you need treatment during this period or while trying to become pregnant, you should use the lowest dose for the shortest time necessary. From the 20th week of pregnancy onwards, ibuprofen may cause kidney problems in your fetus if taken for more than a few days, which can cause low levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing of the blood vessels (ductus arteriosus) in the baby's heart. If you need treatment for more than a few days, your doctor may recommend additional checks.

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.

Driving and using machines

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

Ibuprofen may delay your reaction time, which should be taken into account before performing activities that require greater vigilance, such as driving and using machinery.

This applies to a greater extent to the combination with alcohol.

Ibuprofeno Pharma Combix contains lactose

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

Ibuprofeno Pharma Combix contains sodium

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

3. How to take Ibuprofeno Pharma Combix

Follow the administration instructions of 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 ibuprofen. Do not stop treatment before, as the expected results will not be obtained. Similarly, do not use ibuprofeno for longer than indicated by your doctor.

The lowest 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).

Adults and adolescents over 12 years (≥ 40 kg)

The recommended dose in adults and adolescents from 12 years is one tablet (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.

Use in children

The use of this medication is not recommended in children with less than 40 kg of weight or under 12 years, as the dose of ibuprofen it contains is not suitable for the recommended dosage in these children.

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.

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 that your doctor has prescribed.

Method of administration

This medication is administered orally.

The score line should not be used to break the tablet

To achieve a faster onset of action, the dose can be taken on an empty stomach. It is recommended that patients with sensitive stomachs take ibuprofeno with food.

Take ibuprofeno with enough water. The tablets should be swallowed whole, without chewing, breaking, crushing, or sucking to avoid discomfort in the mouth and throat irritation.

If you think the action of this medication is too strong or too weak, inform your doctor or pharmacist.

If you take more Ibuprofeno Pharma Combix than you should

If you have taken more ibuprofeno 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.

It is recommended to take the package and the prospectus of the medication to the healthcare professional.

Normally, the symptoms of overdose occur 4 to 6 hours after taking ibuprofeno.

Symptoms of overdose may include nausea, stomach pain, vomiting (which may contain bloody sputum), headache, ringing in the ears, confusion, involuntary eye movement, and lack of muscle coordination. At high doses, symptoms of 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. In rare cases, there have been cases of increased blood plasma acidity (metabolic acidosis), decreased body temperature, altered kidney function, stomach and intestinal bleeding, coma, transient loss of breathing (apnea), central nervous system depression, and respiratory system. There have also been cases of cardiovascular toxicity (decreased blood pressure, decreased heart rate, and increased heart rate).

If a severe poisoning has occurred, kidney failure and liver damage may occur. In these cases, the doctor will take the necessary measures.

In case of ingestion of significant amounts, activated charcoal should be administered.

If you forgot to take Ibuprofeno Pharma Combix

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

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

4. Possible adverse effects

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

The adverse effects of medications like ibuprofeno 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.

• Common adverse effects(may affect up to 1 in 10 people): Gastrointestinal bleeding, especially in elderly patients. Nausea, vomiting, diarrhea, flatulence, dyspepsia (disorder of gastrointestinal secretion or motility), constipation, heartburn, abdominal pain, blood in stool, vomiting with blood, headache, dizziness or feeling of instability, fatigue.

• Uncommon adverse effects(may affect up to 1 in 100 people): Gastritis, duodenal ulcers, gastric ulcers, skin redness, itching or tingling of the skin, hives, purpura (purple spots on the skin), skin reactions due to light influence, hypersensitivity, paresthesia (sensation of numbness, tingling, or prickling, more frequent in hands, feet, arms, or legs) and drowsiness, insomnia, anxiety, hearing disorders, vision changes, rhinitis (inflammation of the nasal mucosa), inflammation of the oral mucosa with ulcer formation (mouth sores), gastrointestinal perforations, hepatitis (inflammation of the liver), liver function abnormalities, and jaundice (yellowing of the skin and eyes), asthma, bronchospasm, dyspnea (difficulty breathing). Interstitial nephritis (kidney disorder) and nephrotic syndrome (disorder characterized by protein in the urine and body swelling) and kidney failure. Acute kidney failure and papillary necrosis (especially with prolonged use) associated with increased urea.

• Rare adverse effects(may affect up to 1 in 1,000 people): Disorientation or confusion, depression, irritability, nervousness, psychotic reaction, vertigo, tinnitus (ringing or sounds in the ear), hearing impairment, reversible toxic amblyopia, liver damage, edema (swelling caused by fluid accumulation in tissues), optic neuritis, anaphylactic reaction (in case of severe generalized hypersensitivity reaction, facial swelling, tongue, and larynx, shortness of breath, tachycardia, hypotension (anaphylaxis, angioedema, or severe shock), aseptic meningitis (inflammation of the meninges, which are the membranes that protect the brain and spinal cord, not caused by bacteria). In most cases where aseptic meningitis has been reported with ibuprofeno, the patient had some form of autoimmune disease (such as systemic lupus erythematosus and other collagen diseases), which was a risk factor. The symptoms of aseptic meningitis observed were neck stiffness, headache, nausea, vomiting, fever, or disorientation. Other adverse effects are decreased platelets, decreased white blood cells (which may manifest as frequent infections with fever, chills, or sore throat), decreased red blood cells (which may manifest as difficulty breathing and pale skin), neutropenia (decreased neutrophils), and agranulocytosis (markedly decreased neutrophils), aplastic anemia (bone marrow failure to produce different types of cells), hemolytic anemia (premature destruction of red blood cells). The first symptoms are: fever, sore throat, superficial ulcers in the mouth, pseudogripal symptoms, extreme fatigue, bleeding, and bruising of unknown cause.

• Very rare adverse effects(may affect up to 1 in 10,000 people): Pancreatitis, prolonged bleeding time, lupus erythematosus (joint pain and fever), severe blistering reactions including Stevens-Johnson syndrome (widespread erosions affecting the skin and at least two mucous membranes and lesions of purple color, preferably on the trunk) and toxic epidermal necrolysis (erosions on mucous membranes and painful lesions with necrosis and shedding of the epidermis), erythema multiforme (skin lesion), hair loss. Exceptionally, severe skin infections and soft tissue complications may occur during chickenpox. Liver failure, heart failure, myocardial infarction, hypertension.

Exacerbation of inflammation-related infections has been observed with the use of NSAIDs. If signs of infection or worsening of infection occur during the use of ibuprofeno, it is recommended to consult a doctor as soon as possible.

• Frequency not known(cannot be estimated from available data):

Exacerbation of colitis and Crohn's disease (chronic disease in which the immune system attacks the intestine, causing inflammation that usually produces bloody diarrhea).

A severe skin reaction known as DRESS syndrome (by its English acronym) may occur. The symptoms of DRESS syndrome include: skin rash, lymph node inflammation, and elevated eosinophils (a type of white blood cell). Generalized red scaly rash, with bumps under the skin and blisters located mainly in skin folds, trunk, and upper limbs, accompanied by fever at the start of treatment (acute generalized exanthematous pustulosis). Stop taking ibuprofeno 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

If any of the following adverse effects occur, discontinue treatment and consult your doctor immediately:

• Reddish, 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 may be preceded by fever and flu-like symptoms (exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Generalized skin rash, elevated body temperature, and 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).
• Allergic reactions such as skin rashes, facial swelling, chest tightness, or difficulty breathing.
• Vomiting blood or coffee grounds-like appearance.
• Blood in stool or bloody diarrhea.
• Severe stomach pain.
• Severe or persistent headache.
• Yellowing of the skin (jaundice).
• Signs of severe hypersensitivity (allergy) (see above in this section).
• Swelling of the limbs or fluid accumulation in the arms or legs.

Reporting adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Ibuprofeno Pharma Combix

Keep this medication out of sight and reach of children.

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

Do not store above 30°C.

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

6. Package contents and additional information

Composition of Ibuprofeno Pharma Combix

• The active ingredient is ibuprofeno. Each tablet contains 400 mg of ibuprofeno.
• Other components are:

Core of the tablet:lactose monohydrate, microcrystalline cellulose, pregelatinized cornstarch, sodium croscarmellose, magnesium stearate, anhydrous colloidal silica, and hypromellose.

Coating:hypromellose, propylene glycol (E1520), talc, and titanium dioxide (E171).

Appearance of the product and package contents

Ibuprofeno Pharma Combix 400 mg are film-coated tablets, white, oblong, biconvex, and scored on both sides. The length of the tablets is approximately 17 mm and the width is approximately 8 mm.

They are presented in PVC/PVDC-Aluminum blisters containing 30 film-coated tablets.

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2. Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Rovi Pharma Industrial Services, S.A.

Vía Complutense 140,

E-28805 Alcalá de Henares (Madrid)

Spain

or

Toll Manufacturing Services S.L.

C/ Aragoneses, 2

28108 (Alcobendas-Madrid)

Spain

or

Farmalider, S.A.

C/ Aragoneses, 2

28108 Alcobendas (Madrid)

Spain

Date of the last revision of this prospectus: December 2024

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