Patient Information Leaflet

Neobrufen with Codeine 400 mg/30 mg Film-Coated Tablets

ibuprofen/codeine, hemihydrate phosphate

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

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1. What is Neobrufen with Codeine and what it is used for.

2. What you need to know before taking Neobrufen with Codeine.

3. How to take Neobrufen with Codeine.

4. Possible side effects.

5. Storage of Neobrufen with Codeine.

6. Contents of the pack and additional information

Neobrufen with Codeine contains the active ingredients ibuprofen and codeine phosphate. Ibuprofen belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs) and acts against pain.

This medicine contains codeine. Codeine belongs to a group of medicines called opioid analgesics that act by relieving pain. It may be used alone or in combination with other analgesics, such as paracetamol or ibuprofen.

Neobrufen with Codeine is used in adults for the short-term treatment of moderate intensity pain that is not relieved by other analgesics such as paracetamol or ibuprofen alone.

Do not take Neobrufen with Codeína:

-if you are allergic to ibuprofen, codeína or any of the other components of this medication (listed in section 6).

-if you have had allergic reactions to anti-inflammatory drugs, aspirin or other analgesics, such as asthma, rhinitis, urticaria, angioedema, nasal polyps or gastrointestinal bleeding or perforation,

-if you have had or have a stomach or duodenal ulcer or bleeding, or have had a perforation of the digestive tract,

-if you have severe liver or kidney disease,

-if you vomit blood, have black stools or have bloody diarrhea,

-if you have bleeding or clotting disorders,

-if you have severe asthma or chronic obstructive pulmonary disease,

-if you have severe heart failure,

-if you have respiratory failure or chronic constipation,

-if you have severe dehydration caused by vomiting, diarrhea or inadequate fluid intake

-to relieve pain in children and adolescents (0 to 18 years old) after tonsillectomy or adenoidectomy due to obstructive sleep apnea syndrome,

-if you know that you metabolize codeína very quickly to morphine,

-if you are in the third trimester of pregnancy,

-if you are breastfeeding

Warnings and precautions:

Consult your doctor, pharmacist or nurse before starting to take Neobrufen with Codeína.

It is essential to use the smallest dose that relieves or controls pain. Do not take this medication for longer than necessary to control your symptoms.

Be careful with Neobrufen with Codeína:

Due to ibuprofen:

-If you have had or develop a stomach or duodenal ulcer, bleeding or perforation, which may manifest as severe abdominal pain or persistent and/or black stools, or even without previous warning symptoms. This risk is higher when using high doses and prolonged treatment, in patients with a history of peptic ulcer disease and in elderly patients. In these cases, your doctor will consider the possibility of associating a stomach protector medication;

• If you have Crohn's disease (a chronic disease in which the immune system attacks the intestine, causing inflammation that usually results in bloody diarrhea) or ulcerative colitis, as ibuprofen-containing medications can worsen these conditions;

-If a gastrointestinal hemorrhage or ulcer occurs, treatment should be immediately suspended, so inform your doctor of any unusual abdominal symptoms during treatment and particularly during the initial stages of treatment;

• Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can be associated with a small increase in the risk of heart attack or stroke, especially when used in high doses. Do not exceed the recommended dose or treatment duration.

Due to codeína:

• Codeína should be used with caution in patients with biliary tract disease, including acute pancreatitis, as codeína can cause sphincter of Oddi spasms and decrease bile and pancreatic secretions.
• It should be used with caution in patients with asthma or chronic rhinitis

Contact your doctor if you experience severe abdominal pain and possibly radiating to the back, nausea, vomiting or fever, as these may be symptoms of pancreatitis and biliary system inflammation.

You should especially discuss the treatment with your doctor or pharmacist before taking Neobrufen with Codeína if:

-You are taking medications that alter blood coagulation, such as oral anticoagulants, antiplatelet agents like aspirin. In combined treatment with anticoagulants, your doctor will monitor your prothrombin time (a measure of blood coagulation) during the first few days. You should also inform your doctor about the use of other medications that may increase the risk of bleeding, such as corticosteroids and selective serotonin reuptake inhibitors;

-You have an infection: ibuprofen can mask the signs of an infection, such as fever and pain. Therefore, Neobrufen with Codeína may delay the appropriate treatment of the infection, which may increase the risk of complications. This has been observed in pneumonia caused by bacteria and skin infections related to chickenpox. If you take this medication while you have an infection and the infection symptoms persist or worsen, consult your doctor without delay;

-You are taking other NSAIDs (including Coxib medications), due to the increased risk of ulcers or bleeding;

-You haveheart problems, including heart failure, angina (chest pain) or if you have had a heart attack, coronary artery bypass surgery, peripheral artery disease, or any type of stroke (including a "mini-stroke" or transient ischemic attack "TIA"). High doses of ibuprofen or prolonged treatment have been associated with an increased risk of these adverse events;

-You havehigh blood pressure,diabetes,high cholesterol, a family history ofheart disease or stroke, or if you are asmoker;

-Also, this type of medication can cause fluid retention, especially in patients withheart failure and/or high blood pressure;

-You are over 65 years old, as this increases the tendency to experience adverse reactions;

-Ibuprofen belongs to a group of medications that canreduce fertilityin women. This effect is reversible when the medication is stopped;

-You haveeye problems, you should stop taking the medication and, as a precaution, undergo an eye examination;

-After taking the medication, you observe symptoms ofaseptic meningitis(inflammation of the meninges not caused by bacteria), consult your doctor;

-You havekidney or liver disease. In these cases, you should use the lowest possible dose and the shortest duration. And monitor renal function;

-In case ofdehydration, ensure adequate fluid intake;

-You haveporphyriaintermitens aguda (a rare disorder in which a large amount of porphyrin is eliminated in urine and feces);

-You havechickenpox(a childhood disease), you should not take ibuprofen;

-You havechronic constipation;

-You have anyrespiratory problemsor have a history of asthma, bronchial asthma or allergic diseases such as bronchospasm, urticaria or angioedema, after using other medications;

-You have a history oflow blood pressure,hypothyroidism,seizures, increased intracranial pressure,head injury;

-Thepain or feverpersists for more than 3 days, worsens or new symptoms appear, your doctor should evaluate the clinical situation;

-You may experiencephysical dependence(appearance of physical symptoms when a substance to which the body is accustomed is withdrawn) and tolerance (need to increase the dose to achieve the effect that was previously achieved with a lower dose) with repeated administration of Neobrufen with Codeína due to the codeína content. You should be cautious in patients withchemical dependence(patients who are unable to stop using drugs or alcohol);

• The codeína is metabolized to morphine in the liver by an enzyme. Morphine is the substance that provides pain relief. Some people have a variation of this enzyme, which can affect people in different ways. In some people, morphine is not produced or is produced in very low amounts and will not provide sufficient pain relief. Other people are more likely to experience severe adverse reactions because they produce a very high amount of morphine. If you notice any of the following adverse effects, stop taking this medication and seek medical help immediately: slow or shallow breathing, confusion, drowsiness, small pupils, nausea or vomiting, constipation, loss of appetite;

-Due to its dosage and pharmaceutical form, this medication is only for administration to adults;

-Prolonged use may cause headaches that should not be treated with an increased dose;

-Adverse reactions due to ibuprofen, especially of the gastrointestinal type, may increase with alcohol consumption;

-Severe skin reactions associated with Neobrufen with Codeína treatment have been reported. Stop taking Neobrufen with Codeína and contact your doctor immediately if you experience any skin rash, membrane lesions, blisters or other signs of allergy, as these may be the first signs of a severe skin reaction. See section 4;

-Special control is required in patients undergoing major surgery;

-It may cause allergic reactions without previous exposure to the drug.

-You experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to an increased dose of the medication.

With the use of ibuprofen, signs of drug allergy have been reported, including respiratory problems, facial and neck swelling (angioedema) and chest pain. If you notice any of these signs, stop taking Neobrufen with Codeína immediately and contact your doctor or emergency services.

Respiratory problems related to sleep

Neobrufen with Codeína can cause respiratory problems related to sleep, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, waking up at night due to lack of breath, difficulty maintaining sleep or excessive daytime drowsiness. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.

Consult your doctor, even if any of the above circumstances have occurred at any time.

Children and adolescents

Use in children and adolescents after surgery

Codeína should not be used to relieve pain in children and adolescents after tonsillectomy or adenoidectomy due to obstructive sleep apnea syndrome.

Use in children with respiratory problems

Codeína is not recommended in children with respiratory problems, as it may worsen the symptoms of morphine toxicity.

Other medications and Neobrufen with Codeína

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medication, including those purchased without a prescription, homeopathic, herbal remedies and other health-related products, as it may be necessary to interrupt treatment or adjust the dose of one of them.

In particular, if you are taking some of the following medications, it may be necessary to modify the dose of one of them or interrupt treatment:

Medications listed below may interfere and, therefore, should not be taken together with ibuprofen without consulting your doctor:

Medications that interfere with ibuprofen:

-Should not be used with other analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), including Coxib medications.

-Anticoagulants/antiplatelet agents (e.g. for bleeding problems, e.g. aspirin, warfarin, ticlopidine)

-Medications that lower high blood pressure (ACE inhibitors like captopril, beta-blockers like atenolol and angiotensin II receptor antagonists like losartan)

-Hidantoínas (for seizures) and sulfamidas (antibiotics for infections)

-Lithium (used for manic-depressive disorders)

-Digoxina and cardiac glycosides (used for the heart)

-Metotrexato (used for cancer and rheumatoid arthritis)

-Pentoxifilina (used for circulatory disorders)

-Probenecid and sulfinpirazona (used in patients with gout or with penicillin in infections)

-Quinolonas (antibiotics used in infections)

-Tiazidas (diuretics used to increase urine elimination)

-Sulfonilureas (used to reduce blood glucose levels)

-Ciclosporina, tacrolimus (used to prevent rejection after transplantation)

-Trombolíticos (medications that dissolve or break down blood clots)

-Zidovudina (used in patients infected with the human immunodeficiency virus, causing AIDS)

-Corticosteroids (have many applications because they act against inflammation, such as immunosuppressants in autoimmune diseases and organ transplants, and in diseases that affect metabolism).

-Antidepressants IMAO (for depression)

-Mifepristona (abortifacient medication)

-Inhibidores selectivos de la recaptación de serotonina (used in depression)

-Colestiramina (used to reduce cholesterol)

-Aminoglucósidos (antibiotics)

-Fármacos del tipo de voriconazol o fluconazol (for fungal infections)

-Extractos de hierbas: del árbol Ginkgo biloba.

-Other medications may also affect or be affected by Neobrufen with Codeína treatment. Therefore, always consult your doctor or pharmacist before using Neobrufen with Codeína with other medications.

Medications that interfere with codeína:

-Depressors of the central nervous system(drugs that act on the central nervous system (CNS), used for example to reduce intense pain, in cases of mental illnesses, such as neuromuscular blockers, etc., and when taken together with Neobrufen with Codeína, the effect of the CNS depressant may be increased).

-Should not be administered withalcoholto avoid damaging the stomach and potential potentiation of the codeína depressant effect.

-Inhibitors of CYP2C9 like quinidine (for heart arrhythmias) or fluoxetine, may decrease the effect of codeína.

-The concomitant use of Neobrufen with Codeína with sedatives, such as benzodiazepines or related substances, increases the risk of drowsiness, breathing difficulties (respiratory depression) and coma and may be potentially fatal. Therefore, concomitant use should only be considered when other options are not possible.

However, if your doctor prescribes Neobrufen with Codeína together with sedatives, the dose and duration of concomitant treatment will be limited by your doctor.

- Gabapentina or pregabalina for treating epilepsy or pain caused by nervous system injuries (neuropathic pain)

Inform your doctor of all sedatives you are taking and take exactly the dose recommended by your doctor. It is helpful to inform your friends or family members to be alert to the appearance of the signs and symptoms explained above. Contact your doctor if you experience these symptoms.

Interference with diagnostic tests:

If you are to undergo any diagnostic test (including blood, urine, etc.), inform your doctor that you are being treated with Neobrufen with Codeína, as it may alter the results.

The use of 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 concentrations of urea nitrogen and serum concentrations of creatinine and potassium (may increase)
• Laboratory tests of liver function: increased values of transaminases

Taking Neobrufen with Codeína with food, drinks and alcohol

It is recommended to take Neobrufen with Codeína during or immediately after meals. The administration of ibuprofen with food delays its absorption.

Do not consume alcohol during treatment with this medication due to the increased risk of adverse reactions caused by codeína.

The use of ibuprofen in patients who regularly consume alcohol (three or more alcoholic beverages –beer, wine, liquor…- per day) may cause stomach bleeding.

Pregnancy, breastfeeding and fertility

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

Pregnancy

In the third trimester, the administration of Neobrufen with Codeína is contraindicated,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 predisposition and that of your baby to bleed and delay or prolong delivery more than expected.

Due to the association of the administration of medications like Neobrufen with Codeína with an increased risk of congenital anomalies/abortions,do nottake it during the first 6 months of pregnancy unless absolutely necessary and advised by your doctor. If you need treatment during this period or while trying to become pregnant, you should use the lowest dose for the shortest duration possible. From week 20 of pregnancy onwards, Neobrufen with Codeína may cause kidney problems in your fetus if taken for more than a few days, which may cause low amniotic fluid levels surrounding the baby (oligohydramnios) or narrowing of the blood vessels (ductus arteriosus) in the baby's heart. If you need treatment for a period longer than a few days, your doctor may recommend additional monitoring.

Fertility

For fertile women, it should be noted that medications like Neobrufen with Codeína have been associated with a decrease in the ability to conceive.

Breastfeeding

Consult your doctor or pharmacist before using any medication.

Do not take codeína if you are breastfeeding. Codeína and morphine pass into breast milk.

Childbirth

Do not recommend the administration of Neobrufen with Codeína during childbirth.

Codeína may prolong delivery. Codeína in high doses near delivery may cause respiratory depression in the newborn. Do not recommend its use during delivery if the baby is premature. Opioid analgesics cross the placenta. Administration of medications containing codeína in the days leading up to delivery may cause the newborn to experience withdrawal syndrome. It is recommended to monitor the newborn whose mother took opioids during delivery (FDA category C). If respiratory depression is severe, naloxone may be needed.

Driving and operating machines

Due to ibuprofen: patients who experience dizziness, vertigo, visual disturbances or other central nervous system problems while taking this medication should refrain from driving or operating machinery.If a single dose of ibuprofen or short-term treatment is administered, no special precautions are necessary.

Due to codeína: Neobrufen with Codeína may cause drowsiness, altering mental and/or physical ability. If you notice these effects, avoid driving vehicles or operating machinery.

Use in athletes

This medication contains a component that is metabolized to morphine, so it may produce a positive result in doping control tests.

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

If you have been prescribed Neobrufen with Codeine, before starting treatment and regularly during this, your doctor will explain what you can expect from the use of Neobrufen with Codeine, when and for how long you should use it, when you should contact your doctor and when you should interrupt treatment (see also If you interrupt treatment with Neobrufen with Codeine).

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

The 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).

Adults

The recommended dose is 1 tablet (400 mg of ibuprofen, 30 mg of codeine phosphate hemihydrate) every 4-6 hours according to the intensity of the pain. No more than 6 tablets (2,400 mg of ibuprofen, 180 mg of codeine phosphate hemihydrate) should be taken within 24 hours.

The tablets should be swallowed whole, with a glass of water, without chewing, breaking, crushing or sucking to avoid mouth discomfort and throat irritation.

This medication is administered orally.

It is advisable to take the medication with meals or with some food. Any patient who notes digestive discomfort before taking the medication should consult a doctor.

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

This medication should not be taken for more than 3 days. If the pain does not improve after 3 days, ask your doctor for advice.

Use in children and adolescents

Do not administer to minors under 18 years old.

Use in people over 65 years old

Older people are more prone to its adverse effects, so it may be necessary to reduce the dose. Consult your doctor.

Patients with kidney and/or liver diseases

If you have a 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 take more Neobrufen with Codeine than you should

If you have taken more Neobrufen with Codeine than you should, or if a child has accidentally ingested the medication, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested, or go to the nearest hospital to inform yourself 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 contain blood-stained mucus), headache, ringing in the ears, confusion, involuntary eye movement, and muscle coordination failure. At high doses, symptoms of drowsiness, chest pain, palpitations, loss of consciousness, seizures (mainly in children), weakness, and dizziness, blood in the urine, chills, and breathing difficulties have been reported.

Metabolic acidosis (a disorder that produces an increase in blood plasma acidity) has been rarely reported, hypothermia (body temperature below 35°C), renal effects, gastrointestinal bleeding, coma, apnea (cessation of respiratory signal for at least 10 seconds), and depression of the central nervous system and respiratory systems. Cardiovascular toxicity, including hypotension (lower than usual blood pressure), bradycardia (decrease in heart rate) and tachycardia (heart rate above 100 beats per minute), has been reported. In cases of significant overdose, renal failure and liver damage are possible.

The symptoms reported with codeine overdose include drowsiness, skin rash, pupil constriction, vomiting, tingling, ataxia (decrease in ability to coordinate body movements), and skin swelling. Renal failure and some deaths have also been reported. Other symptoms observed are initial excitement, anxiety, insomnia, and later in some cases, headache, blood pressure alterations, arrhythmias (heart rhythm alterations), dry mouth, hypersensitivity reactions (allergy), tachycardia (heart rate above 100 beats per minute), seizures, gastrointestinal disturbances, and nausea.

If a severe intoxication has occurred, the doctor will take the necessary measures. There is no specific antidote for ibuprofen with codeine overdose.

In case of ingestion of significant amounts, activated charcoal should be administered. If central nervous system depression has occurred, artificial respiration, oxygen administration, and naloxone administration are necessary.

If you forgot to take Neobrufen with Codeine

Do not take a double dose to compensate for the missed doses.

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

If you interrupt treatment with Neobrufen with Codeine

Due to the codeine content, there is a risk of possible withdrawal effects when suspending treatment (appearance of physical symptoms when removing a substance to which the body is accustomed).

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

The assessment of the frequency of adverse reactions is based on the following criteria: Very common: may affect more than 1 in 10 people; Common: may affect up to 1 in 10 people; Uncommon: may affect up to 1 in 100 people; Rare: may affect up to 1 in 1,000 people; Very rare: may affect up to 1 in 10,000 people; Frequency not known: cannot be estimated from available data.

The side effects that may appear due to the content of ibuprofen are:

-Gastrointestinal disorders

The most common side effects that occur with medicines like Neobrufen with Codeine are gastrointestinal:

Common: nausea, vomiting, diarrhea, flatulence, constipation, heartburn, abdominal pain, blood in stool, vomiting blood, gastrointestinal bleeding.

Uncommon: gastritis, duodenal ulcer, stomach ulcer, mouth ulcers (aphthous stomatitis), gastrointestinal perforation.

Very rare: pancreatitis.

Frequency not known: ulcerative colitis, Crohn's disease (a chronic condition in which the immune system attacks the intestine, causing inflammation that usually results in bloody diarrhea).

Peptic ulcers, gastrointestinal bleeding, perforations (in some cases fatal), especially in elderly patients, may occur.

-Immune system disorders

Rare: anaphylactic reaction (allergic reaction to a substance whose first administration did not cause any disturbance).

Reactions of hypersensitivity have been observed after treatment with NSAIDs. This may consist of (a) a non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity such as asthma, exacerbated asthma, bronchospasm, or dyspnea, or (c) various skin alterations, including various types of rashes, pruritus, urticaria, purpura, and angioedema.

-Skin and subcutaneous tissue disorders

Common:skin rash.

Uncommon:itching, urticaria, purpura (purple spots on the skin), angioedema (transient edema in areas of the skin, mucous membranes, or sometimes in viscera), photosensitivity reaction (abnormal skin response to exposure to light).

Very rare: various severe skin reactions, such as bullous dermatosis (including Stevens-Johnson syndrome (widespread erosions affecting the skin and two or more mucous membranes and lesions of purple color, preferably on the trunk)), toxic epidermal necrolysis (erosions in mucous membranes and painful lesions with necrosis and skin detachment)and erythema multiforme (allergic reaction with general discomfort, fever, joint pain, and skin lesions).

A severe skin reaction known as DRESS syndrome (by its English acronym) may occur. Symptoms of DRESS syndrome include: skin rash, lymph node inflammation, and elevated eosinophils (a type of white blood cell).

A generalized red scaly rash, with bumps under the skin and localized blisters mainly on skin folds, trunk, and upper limbs, accompanied by fever at the beginning of treatment (generalized acute pustular exanthema). Stop taking Neobrufen with Codeine if you experience these symptoms and seek medical attention immediately. See section 2.

-Infections and infestations:

Uncommon:rhinitis (inflammation of the nasal mucosa).

Rare:aseptic meningitis(inflammation of the meninges that are the membranes protecting the brain and spinal cord, not caused by bacteria).

Exacerbation of inflammatory conditions related to infections (e.g., development of necrotizing fasciitis) coinciding with the use of NSAIDs has been described. If signs of infection or these worsen during the use of ibuprofen, it is recommended to consult a doctor as soon as possible.

-Blood and lymphatic system disorders:

Rare: leukopenia(decrease in white blood cells, may manifest as frequent infections with fever, chills, or sore throat), thrombocytopenia (decrease in platelets in the blood), aplastic anemia(insufficiency of the bone marrow to produce different types of cells), neutropenia (decrease in granulocytes that predispose to having infections), agranulocytosis(severe decrease in granulocytes), hemolytic anemia (premature destruction of red blood cells).

-Psychiatric disorders:

Uncommon: insomnia, anxiety.

Rare: depression, confusion.

-Nervous system disorders:

Common: headache, dizziness.

Uncommon: paresthesia (numbness, tingling, aching, etc. more frequent in hands, feet, arms, or legs), somnolence.

Rare: optic neuritis (inflammation of the optic nerve).

-Eye disorders:

Uncommon: visual deterioration, blurred vision, decreased visual acuity or changes in color perception that resolve spontaneously.

Rare: toxic optic neuropathy (degeneration of the retina).

-Ear and labyrinth disorders:

Uncommon: hearing loss, vertigo, tinnitus.

-Hepatobiliary disorders:

Uncommon: hepatitis (inflammation of the liver), jaundice (yellowing of the skin and eyes), abnormal liver function.

Very rare: liver failure (severe deterioration of the liver).

-Renal and urinary disorders:

Uncommon: tubulointerstitial nephritis (kidney disorder), nephrotic syndrome (a disorder characterized by protein in the urine and body swelling) and renal failure (sudden loss of kidney function).

-Respiratory, thoracic and mediastinal disorders:

Uncommon: asthma, bronchospasm (bronchiole constriction), dyspnea (difficulty breathing).

-Musculoskeletal and connective tissue disorders:

Rare: neck stiffness.

-General disorders and administration site conditions:

Common: fatigue.

Rare: edema (fluid retention).

• Cardiac disorders:

Uncommon: heart failure, myocardial infarction.

Frequency not known: chest pain, which may be a sign of a severe allergic reaction possibly called Kounis syndrome.

• Vascular disorders:

Uncommon: hypertension.

Medicines like Neobrufen with Codeine may be associated with a moderate increase in the risk of suffering a heart attack ("myocardial infarction") or stroke at high doses (2,400 mg daily) and in prolonged treatments. On the other hand, low doses (less than or equal to 1,200 mg daily of ibuprofen) are not associated with an increased risk of myocardial infarction.

In the treatment with NSAIDs, the following adverse effects have been referred to: edema (fluid retention), hypertension (elevated blood pressure) and coronary insufficiency (heart's inability to pump blood in adequate volumes for normal functioning).

The side effects that may appear due to the content of codeine are the characteristic effects of opioids

The frequency and severity of these effects are determined by the dose, duration of treatment, and individual sensitivity. These include:

• Respiratory, thoracic and mediastinal disorders

bronchospasm, respiratory depression.

-Psychiatric disorders:

confusion, agitation.

Dependence may occur, especially with high doses of codeine for a prolonged period.

-Nervous system disorders:

dizziness and somnolence.

-Cardiac disorders

palpitations

-Gastrointestinal and hepatobiliary disorders:

constipation, nausea, vomiting.

Frequency not known: symptoms related to inflammation of the pancreas (pancreatitis) and the biliary system (a problem affecting a valve of the intestines, called Oddi's sphincter dysfunction), e.g., severe abdominal pain and possibly radiated to the back, nausea, vomiting, or fever

• Immune system disorders:

allergic rash, urticaria, allergic reactions.

-Skin and subcutaneous tissue disorders

itching, excessive sweating.

-Renal and urinary disorders:

urinary retention.

-General disorders and administration site conditions:

Tolerance to the drug (need to increase the dose to achieve the effect that was previously achieved with a lower dose) may occur, especially with high doses of codeine for a prolonged period.

Neobrufen with codeine, especially when taken in doses higher than recommended or for a prolonged period, may cause kidney damage, which becomes unable to effectively eliminate acidic substances from the blood through urine (tubular acidosis). It may also significantly reduce potassium levels in the blood (see section 2). This is a very serious condition that requires immediate treatment. Symptoms and signs include muscle weakness and dizziness.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is possible adverse reactions that do not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use: https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

No special storage conditions are required.

Store this medication in a secure location that is inaccessible to others. It may cause severe injuries and be fatal to individuals who have not been prescribed it.

Do not use this medication after the expiration date that appears on the packaging after CAD or EXP. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Neobrufen with Codeine

The active principles are ibuprofen and hemihydrate codeine phosphate.

Each tablet contains 400 mg of ibuprofen and 30 mg of hemihydrate codeine phosphate.

The other components (excipients) are: potato starch glycolate, microcrystalline cellulose, anhydrous colloidal silica, pregelatinized cornstarch, L-Leucine, talc, 30% dispersion of methacrylic acid-ethyl acrylate copolymer (1:1) (Eudragit L30 D55), titanium dioxide, Macrogol 6000, simethicone emulsion, and sodium carboxymethylcellulose.

Appearance of the product and contents of the packaging

This medication is presented in the form of coated tablets with a notch on one face to make them easier to swallow. Each package contains 30 or 500 coated tablets conditioned in Al/PVDC-PVC/PVDC blister.

Holder of the marketing authorization and responsible for manufacturing

Holder:

Viatris Healthcare Limited

Damastown Industrial Park

Mulhuddart, Dublin 15

Dublin

Ireland

Responsible for manufacturing:

Farmasierra Manufacturing S.L.

Carretera de Irún km 26,200

San Sebastián de los Reyes

28700 - Madrid

Spain

You can request more information about this medication by contacting the local representative of the holder of the marketing authorization :

Viatris Pharmaceuticals, S.L.

C/ General Aranaz, 86

28027 Madrid

Spain

Last review date of this leaflet: December 2024.

The detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) https://www.aemps.gob.es/ ”