Ibuprofen Zentiva Italia: detailed information

PACKAGE LEAFLET: INFORMATION FOR THE USER

IBUPROFENE ZENTIVA ITALIA 200 mg film-coated tablets

Ibuprofen
Equivalent medicine
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.
Always take this medicine exactly as described in this leaflet or as your doctor or
pharmacist has instructed you.

Keep this leaflet. You may need to read it again.
If you need more information or advice, consult your pharmacist.
If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.
Consult your doctor if you do not notice any improvement or if you experience worsening of symptoms after 3 days (in children and adolescents) or after 7 days (in adults) of treatment.

Contents of this leaflet:

What IBUPROFENE ZENTIVA ITALIA 200 mg is and what it is used for
What you need to know before taking IBUPROFENE ZENTIVA ITALIA 200 mg
How to take IBUPROFENE ZENTIVA ITALIA 200 mg
Possible side effects
How to store IBUPROFENE ZENTIVA ITALIA 200 mg
Contents of the pack and other information

1. WHAT IBUPROFEN ZENTIVA ITALIA 200 MG IS AND WHAT IT IS USED FOR

IBUPROFEN ZENTIVA ITALIA 200 mg contains ibuprofen, a medicine belonging to a class of medicines called NSAIDs (non-steroidal anti-inflammatory drugs) that work by reducing pain, inflammation, and fever.
IBUPROFEN ZENTIVA ITALIA 200 mg is used in adults, adolescents, and children from 6 years of age to provide relief in the following cases:

Mild to moderate pain (such as headache, including migraine-related headache, toothache, and fever).

IBUPROFEN ZENTIVA ITALIA 200 mg is used in adults and adolescents from 12 years of age to provide relief in the following case:

Menstrual pain (primary dysmenorrhea).

Consult your doctor if you do not feel better or if you feel worse after 3 days (in children and adolescents) or after 7 days (in adults).

2. WHAT YOU SHOULD KNOW BEFORE TAKING IBUPROFENE ZENTIVA ITALIA 200 MG

DO NOT TAKE IBUPROFENE ZENTIVA ITALIA 200 mg

if you are allergic to ibuprofen or to any of the other ingredients of this medicine (listed in section 6). If you are allergic to other non-steroidal anti-inflammatory drugs (NSAIDs)
if you have experienced allergic reactions such as asthma, excessive nasal discharge (rhinitis), itchy skin rashes (urticaria), or swelling of the lips, face, tongue, or throat (angioedema) after taking medicines containing acetylsalicylic acid or other painkillers or anti-inflammatory drugs (NSAIDs).
if you have previously experienced stomach or intestinal damage (ulcer) or bleeding related to prior use of painkillers or anti-inflammatory medicines (NSAIDs).
if you currently suffer from stomach or intestinal ulcer or bleeding, or have had two or more such episodes in the past.
if you currently suffer from or have previously suffered from ulcerative colitis, Crohn's disease, peptic ulcer, or recurrent gastrointestinal bleeding (defined as two or more distinct episodes of confirmed ulceration or hemorrhage).
if you suffer from or have suffered from a congenital disorder affecting porphyrin metabolism (e.g., acute intermittent porphyria).
chronic alcoholism (14 to 20 drinks/week or more).
if you suffer from severe liver (hepatic insufficiency), kidney (renal insufficiency), or heart problems (heart failure), or have coronary artery disease (coronary heart disease).
if you are in the last three months of pregnancy or are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).
if you are experiencing significant fluid loss from the body (dehydration) caused by vomiting, diarrhea, or insufficient fluid intake.
if you have active bleeding (including in the brain).
if you suffer from an unknown-origin disease causing abnormal blood cell formation (dysmyelopoiesis).
if you are under 6 years of age.

Warnings and precautions – take special care with IBUPROFENE ZENTIVA ITALIA 200 mg
Serious skin reactions have been reported in association with treatment with IBUPROFENE ZENTIVA ITALIA, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and generalized acute exanthematous pustulosis (GAEP). Discontinue use of IBUPROFENE ZENTIVA ITALIA and contact your doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.

Signs of an allergic reaction to this medicine, including breathing difficulties, facial and neck swelling (angioedema), and chest pain, have been reported with ibuprofen. Immediately discontinue treatment with IBUPROFENE ZENTIVA ITALIA and contact your doctor or emergency medical services immediately if you notice any of these signs.
Anti-inflammatory/pain-relief medicines such as ibuprofen may be associated with a small increased risk of heart attack or stroke, especially when administered at high doses. Do not exceed the recommended dose or duration of treatment.

Consult your doctor or pharmacist before taking IBUPROFENE ZENTIVA ITALIA 200 mg if:

you have heart problems including heart attack, angina (chest pain), or a history of heart attack, coronary bypass surgery, peripheral arterial disease (poor circulation to legs or feet due to narrowed or blocked arteries), or any type of stroke (including "mini-stroke" or TIA, transient ischemic attack);
you have high blood pressure, diabetes, high cholesterol, a family history of heart disease or stroke, or if you are a smoker.
you suffer from congestive heart failure
you suffer from an autoimmune disease called systemic lupus erythematosus (SLE) or other diseases affecting the immune system
you suffer from an inherited disorder affecting hemoglobin, a substance that carries oxygen in the blood (acute intermittent porphyria)
you are significantly dehydrated (caused by vomiting, diarrhea, or inadequate fluid intake)
you suffer from chronic inflammatory bowel diseases such as ulcerative colitis (inflammation of the intestine with ulcers), Crohn’s disease (inflammation of the digestive tract), or other stomach and intestinal disorders
you have previously suffered from stomach or intestinal ulcer, particularly if complicated by perforation or accompanied by bleeding. Immediately report any unusual stomach or intestinal symptoms (especially bleeding or ulceration) to your doctor, particularly if these symptoms occur at the beginning of treatment. These symptoms are more likely in elderly patients. See section “Possible side effects”
you suffer from disorders of blood cell formation (hematopoietic disorder)
you suffer from disorders affecting normal blood clotting mechanisms
you have allergies, nasal mucosa disease (hay fever), asthma, chronic nasal swelling (adenoids), or chronic obstructive respiratory diseases (asthma)
you suffer from liver, kidney, heart problems or high blood pressure (especially if you are elderly)
you have recently undergone surgery
you are in the first six months of pregnancy
you are breastfeeding
you experience blurred vision or other eye symptoms, skin rash, weight gain, or fluid retention (edema)
you have an infection – see section «Infections» below.

Respiratory disorders
Special precautions must be taken in asthmatic patients or those with a history of asthma, bronchial diseases, chronic rhinitis, or respiratory diseases, as ibuprofen may trigger bronchospasm, urticaria, or angioedema in these patients.

Allergic reactions
Severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed, although rarely. At the first sign of a hypersensitivity reaction after taking Ibuprofene Zentiva Italia, treatment must be discontinued. Necessary medical measures, depending on symptoms, should be initiated by specialized personnel. Caution is required in patients who have experienced allergic or hypersensitivity reactions to other substances, as they may have an increased risk of hypersensitivity reactions to ibuprofen. Caution is also required in patients with hay fever, nasal polyps, or chronic obstructive respiratory infections, as this increases the risk of allergic reactions. These may present as asthma attacks (so-called analgesic-induced asthma), Quincke’s edema, or urticaria.

Cardiac, renal or hepatic disorders
Precautions are necessary in patients with renal, hepatic, or cardiac insufficiency, as NSAIDs may worsen renal function. Habitual concomitant use of multiple painkillers further increases this risk. In such patients, the dose should be as low as possible and for the shortest possible duration (see section “Do not take Ibuprofene Zentiva Italia”).

Effects on kidneys
At the beginning of treatment, ibuprofen, like other NSAIDs, should be administered cautiously in patients with significant dehydration (risk of renal failure, especially in dehydrated children, adolescents, and elderly patients). As with other NSAIDs, prolonged administration of ibuprofen has caused renal papillary necrosis and other pathological renal changes. Cases of renal toxicity have occurred in patients where prostaglandins play a compensatory role in maintaining renal perfusion. In these patients, administration of NSAIDs may cause dose-dependent reduction in prostaglandin production and, secondarily, reduced renal blood flow, potentially leading to overt renal decompensation. Most patients at risk for this reaction are those with renal dysfunction, heart failure, liver disease, those taking diuretics and ACE inhibitors, and elderly patients.
Discontinuation of NSAID therapy is generally followed by return to the pre-treatment state.

Aseptic meningitis
Rarely, aseptic meningitis has been observed in patients treated with ibuprofen. Although it is more likely to occur in patients with systemic lupus erythematosus and connective tissue diseases, cases have been reported in patients without underlying chronic conditions.

Hematological effects
Ibuprofen, like other NSAIDs, may inhibit platelet aggregation and prolong bleeding time in normal patients.

Exceptionally, chickenpox may lead to severe complications such as serious skin or soft tissue infections. To date, the role that NSAIDs may play in worsening these symptoms or infections cannot be excluded. Therefore, it is recommended to avoid the use of Ibuprofene Zentiva Italia in case of chickenpox.

Elderly population
Elderly patients have a higher frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which can be fatal.

Gastrointestinal bleeding, ulceration and perforation:
Ibuprofen should be administered cautiously in patients with a history of peptic ulcer or other gastrointestinal disorders, as these conditions may be exacerbated. Cases of potentially fatal gastrointestinal bleeding, ulceration, and perforation have been reported with all NSAIDs at various stages of treatment, with or without warning symptoms or history of serious gastrointestinal events. The risk of bleeding, ulceration, or perforation is higher with higher doses of ibuprofen, in patients with a history of peptic ulcer, especially if associated with bleeding or perforation, and in elderly patients. In these patients, treatment should be initiated with the lowest effective dose. Concomitant administration of protective agents (e.g., misoprostol or proton pump inhibitors) should be considered in these patients, as well as in those requiring concomitant low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk. Precautions should be taken in patients requiring concomitant use of other drugs that may increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid. In case of gastrointestinal bleeding or ulceration in patients taking Ibuprofene Zentiva Italia, treatment must be discontinued. Concomitant administration of Ibuprofene Zentiva Italia with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to increased risk of ulceration or hemorrhage. Patients with a history of gastrointestinal disorders, particularly the elderly, should report unusual abdominal symptoms (especially gastrointestinal bleeding) early in treatment.

Infections
IBUPROFENE ZENTIVA ITALIA may mask symptoms of infections such as fever and pain. Therefore, Ibuprofene Zentiva Italia may delay appropriate treatment of infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Medicines such as IBUPROFENE ZENTIVA ITALIA 200 mg may be associated with a small increased risk of thrombus formation (arterovenous thrombotic events) such as heart attack (“myocardial infarction”) or stroke (lack of blood flow to the brain): this risk is more likely with high doses and prolonged treatment.
Ibuprofen may temporarily increase the tendency to bleed.

Skin reactions
Serious skin reactions have been reported in association with treatment with IBUPROFENE ZENTIVA ITALIA. Discontinue use of IBUPROFENE ZENTIVA ITALIA and consult your doctor immediately if a skin rash, mucosal lesions, blisters, or other signs of allergy appear, as they may be early signs of a very serious skin reaction. See section 4.

Children and Adolescents
In dehydrated children and adolescents, there is a risk of impaired renal function.

Other medicines and IBUPROFENE ZENTIVA ITALIA 200 mg
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
IBUPROFENE ZENTIVA ITALIA 200 mg may affect or be affected by other medicines. For example:

other NSAIDs and/or acetylsalicylic acid, used to treat pain and inflammation (such as COX-2 inhibitors or other NSAIDs). See section “Do not use IBUPROFENE ZENTIVA ITALIA 200 mg if”.
corticosteroids, used to treat inflammation
medicines with anticoagulant effects (i.e., substances that thin the blood, preventing clot formation, e.g., aspirin/acetylsalicylic acid, warfarin, ticlopidine): NSAIDs may enhance the effects of anticoagulants such as warfarin. Acetylsalicylic acid: as with other NSAIDs, co-administration of ibuprofen and acetylsalicylic acid is generally not recommended due to potential increased adverse effects.
medicines that lower blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, angiotensin II receptor antagonists such as losartan)
other anticoagulant medicines, such as heparin and clopidogrel: increased risk of gastrointestinal bleeding with NSAIDs
methotrexate: NSAIDs may reduce its elimination and consequently increase plasma levels of methotrexate.
cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides.
digoxin, used to treat various heart conditions
phenytoin (used to treat epilepsy);
lithium: NSAIDs may reduce lithium elimination
diuretics, including potassium-sparing diuretics, which increase urine production.
Cholestyramine: concomitant administration of ibuprofen and cholestyramine may reduce ibuprofen absorption from the gastrointestinal tract. However, the clinical significance is not known.
antibiotics such as aminoglycosides: NSAIDs may reduce aminoglycoside elimination. Quinolone antibiotics: patients taking NSAIDs and quinolones may be at higher risk of developing seizures.
SSRIs, medicines used to treat depression
moclobemide, used to treat depressive illness or social phobia
cyclosporine: co-administration of NSAIDs and cyclosporine increases the risk of nephrotoxicity.
Antihypertensives, beta-blockers, and diuretics: NSAIDs may reduce the effectiveness of these medicines. Diuretics may increase the risk of NSAID-induced nephrotoxicity. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant administration of an ACE inhibitor, beta-blocker, or angiotensin II antagonist with agents that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be used with caution, especially in the elderly. Patients should be adequately hydrated, and monitoring of renal function should be considered after initiation of therapy and periodically during concomitant therapy.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors:
Concomitant administration of Ibuprofene Zentiva Italia with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to potential additive effects. Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.
tacrolimus: possible increased risk of nephrotoxicity when an NSAID is administered with tacrolimus.
Zidovudine: increased risk of hematological toxicity when an NSAID is administered with zidovudine
Ritonavir, used in the treatment of HIV patients
Ginkgo Biloba: may increase the risk of bleeding with NSAIDs.
Mifepristone: NSAIDs may reduce the effects of mifepristone
probenecid or sulfinpyrazone: drugs containing probenecid or sulfonpyrazone may delay ibuprofen elimination.
sulfonylureas: NSAIDs may enhance the effects of sulfonylurea drugs (rare cases of hypoglycemia have been reported in patients receiving sulfonylurea and ibuprofen simultaneously).
corticosteroids, used to treat inflammation
bisphosphonates, used to treat certain bone diseases (osteoporosis and Paget's disease) and to reduce elevated blood calcium levels
oxpentifylline/pentoxifylline, used to treat a blood circulation disorder in arms or legs
baclofen, a muscle relaxant.

Other medicines may also influence or be influenced by treatment with IBUPROFENE ZENTIVA ITALIA 200 mg. Therefore, always consult your doctor or pharmacist before using IBUPROFENE ZENTIVA ITALIA 200 mg with other medicines.

IBUPROFENE ZENTIVA ITALIA 200 mg with food, drinks and alcohol
Avoid drinking alcohol, as it may increase the undesirable effects of IBUPROFENE ZENTIVA ITALIA 200 mg, particularly those affecting the stomach, intestine, or brain. See section “Driving and use of machines”.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
DO NOT take IBUPROFENE ZENTIVA ITALIA 200 mg during the last three months of pregnancy, as it may harm the fetus or cause problems during delivery. It may cause kidney and heart problems in the fetus. It may affect your and your baby's tendency to bleed and delay or prolong labor more than expected.
You should not take IBUPROFENE ZENTIVA ITALIA during the first six months of pregnancy unless absolutely necessary and under medical advice.
If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible time should be used. From week 20 of pregnancy, IBUPROFENE ZENTIVA ITALIA may cause kidney problems in the fetus if taken for more than a few days, thereby reducing the levels of amniotic fluid surrounding the baby (oligohydramnios) or causing narrowing of a blood vessel (ductus arteriosus) in the baby's heart. If treatment is needed for more than a few days, your doctor may recommend additional monitoring.

Breastfeeding
Ibuprofen passes into breast milk in very small amounts and it is generally not necessary to stop breastfeeding during short-term treatment. However, if prolonged treatment is prescribed, early weaning should be considered.

Fertility
This medicine belongs to a group of medicines (NSAIDs) that may impair fertility in women. This effect is reversible upon discontinuation of the medicine.

Driving and use of machines
Ibuprofen generally does not have undesirable effects on the ability to drive vehicles or operate machinery. However, at high doses, undesirable effects such as fatigue, drowsiness, dizziness (reported as common) and visual disturbances (reported as uncommon) may occur, and in isolated cases, the ability to drive or operate machinery may be impaired. The effect is enhanced by concomitant alcohol intake.

IBUPROFENE ZENTIVA ITALIA contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. HOW TO USE IBUPROFEN ZENTIVA ITALIA 200 MG

Use this medicine exactly as described in this leaflet or as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The lowest effective dose for the shortest duration necessary to relieve symptoms should be used.
If you have an infection, contact your doctor immediately if symptoms (e.g. fever and pain) persist or worsen (see section 2).
Adverse effects can be minimized by using the lowest effective dose for the shortest duration needed to control symptoms. Therefore, do not exceed the recommended dose or duration of treatment.

How much should you take?
The dose of ibuprofen depends on age and body weight.

Adults and adolescents over 12 years of age (≥ 40 kg):

Fever and mild to moderate pain

1-2 tablets taken as a single dose or 3-4 times daily at intervals of 4-6 hours.
For headache due to migraine, the dosage is: 2 tablets taken as a single dose; if necessary, continue with 2 tablets at intervals of 4-6 hours.
The maximum daily dose must not exceed 6 tablets (1200 mg).

Menstrual pain (primary dysmenorrhea)

1-2 tablets 1-3 times daily at intervals of 4-6 hours, as needed. The maximum daily dose must not exceed 6 tablets (1200 mg).

Elderly
If you are elderly, you should always consult your doctor before using IBUPROFEN ZENTIVA ITALIA 200 mg, as you are more likely to experience adverse effects, particularly gastrointestinal bleeding and perforation, which can be fatal. Your doctor will determine the appropriate dose for you.

If you have kidney or liver problems
Always consult your doctor before taking IBUPROFEN ZENTIVA ITALIA 200 mg. Your doctor will determine your dose, the duration of treatment, and will monitor your kidney and liver function.

Use in children
Children 6-12 years of age (>20 kg):

Children 6-9 years of age (20-29 kg): 1 tablet 1-3 times daily at intervals of 4-6 hours, as needed. The maximum daily dose must not exceed 3 tablets per day (600 mg).
Children 10-12 years of age (30-40 kg): 1 tablet 1-4 times daily at intervals of 4-6 hours, as needed. The maximum daily dose must not exceed 4 tablets per day (800 mg).

How to take this medicine

Swallow the tablets with a glass of water during or after meals.
The tablets may be swallowed whole or divided in half (scored tablets) to facilitate swallowing or to adjust the dose.

For how long

This medicine is intended only for short-term treatment, not exceeding 7 days. If symptoms persist or worsen, consult your doctor.
If use of the medicine is required for more than 3 days in children and adolescents, or if symptoms worsen, consult your doctor.

If you take more IBUPROFEN ZENTIVA ITALIA 200 mg than you should
If you have taken more IBUPROFEN ZENTIVA than you should, or if your child has taken this medicine by mistake, contact a doctor or the nearest hospital immediately for advice on the risk and actions to take.
Symptoms of overdose may include nausea, stomach ache, vomiting (possibly with traces of blood), headache, tinnitus, confusion, and uncontrolled eye movements.
At high doses, drowsiness, chest pain, palpitations, loss of consciousness, convulsions (especially in children), weakness, dizziness, blood in urine, low potassium levels in blood, feeling cold, and breathing difficulties may occur.
Other symptoms may include: agitation, disorientation, abdominal pain, deep sleep with reduced response to normal stimuli (lethargy), lowered body temperature (hypothermia), kidney problems, stomach and intestinal bleeding, deep unconsciousness (coma), temporary cessation of breathing (apnea), diarrhoea, reduced activity of the nervous system and respiratory depression.
Additional symptoms may include: excitement, fainting, low blood pressure (hypotension), decreased or increased heart rate (bradycardia or tachycardia).
If you take significantly high doses of ibuprofen, severe kidney (renal failure) and liver damage may occur. In cases of severe poisoning, metabolic acidosis (increased acid levels in the blood) may occur.
Symptoms of overdose may appear within 4–6 hours after taking ibuprofen.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

If you forget to take IBUPROFEN ZENTIVA ITALIA 200 mg
If you forget a dose, take it as soon as possible, unless there are less than 4 hours until the next scheduled dose.
Do not take a double dose to make up for the missed dose.

If you stop taking IBUPROFEN ZENTIVA ITALIA 200 mg
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Infections and infestations
Exacerbations of inflammation related to skin infections (e.g. development of necrotizing fasciitis) occurring
concurrently with the use of NSAIDs. If signs of infection occur or worsen during ibuprofen use, patients should
be advised to seek immediate medical advice.

Skin and subcutaneous tissue disorders
In rare cases, severe skin infections and soft tissue complications may occur during varicella infection (see also infections and infestations).
of the soft tissues (see also infections and infestations).

Cardiovascular and cerebrovascular effects
Clinical studies suggest that administration of ibuprofen, especially at high doses (2400 mg daily) and
in long-term treatment, may be associated with a slight increase in the risk of arterial thrombotic
events (e.g. myocardial infarction or stroke) (see “Warnings and precautions”).

Gastrointestinal disorders
The most frequently observed adverse reactions are of a gastrointestinal nature. Following the
administration of these medicinal products, nausea, dyspepsia, vomiting, haematemesis, flatulence,
abdominal pain, diarrhoea, constipation, melaena, aphthous stomatitis, gastrointestinal bleeding, exacerbation of

colitis and Crohn's disease. Less frequently, cases of gastritis, duodenal and gastric ulcer, and
gastrointestinal perforation have been observed.

Adverse reactions are more likely with higher doses and longer duration of treatment.
The adverse reactions listed below are categorized according to their frequency of occurrence.
The following adverse reactions are important and require immediate attention if they occur. STOP treatment with IBUPROFENE ZENTIVA ITALIA 200 mg and consult your doctor immediately if you experience any of the following symptoms:

Very common (affects more than 1 in 10 people):

Gastrointestinal disorders such as heartburn (pyrosis), indigestion (dyspepsia), abdominal pain, nausea, vomiting, excessive gas in the stomach (flatulence), diarrhea, constipation.

Common (affects 1 to 10 in 100 people):

Intestinal inflammation and worsening of colonic inflammation, a part of the intestine (colitis), and of the gastrointestinal tract (Crohn's disease)
Complications of diverticula, small pouches that form in the lower part of the intestine (perforation or fistula)
Stomach and intestinal damage (gastrointestinal ulcers), sometimes with bleeding, which may cause anemia (reduction in hemoglobin in the blood, the substance that carries oxygen in the blood), melena (black stools), hematemesis (blood in vomit), ulcerative stomatitis (inflammation of the oral mucosa), colitis. These effects generally increase with higher doses of ibuprofen or if you are taking certain other medicines (See section “Other medicines and IBUPROFENE ZENTIVA ITALIA 200 mg”). Elderly patients are more prone to gastrointestinal bleeding and perforation. These effects may also be fatal.
Headache
Drowsiness
Dizziness
Vertigo
Fatigue
Restlessness
Insomnia
Irritability

Uncommon (affects 1 to 10 in 1,000 people):

Inflammation of the stomach (gastritis)
Kidney problems (nephrotic syndrome), development of edema (swelling due to fluid accumulation), leg swelling, inflammation of the kidneys (interstitial nephritis), reduced kidney function (renal failure)
Increased sensitivity of the skin to sunlight (photosensitivity)
Vision disturbances
Insomnia
Anxiety
Paresthesia
Hearing impairment
Excessive nasal secretion (rhinitis)
Breathing difficulties (bronchospasm)
Allergic reactions such as skin rashes (exanthema and urticaria), itching, skin redness due to capillary rupture (purpura), asthma attacks sometimes accompanied by low blood pressure (hypotension)

Rare (affects 1 to 10 in 10,000 people):

Depression
Confusional state
Hallucinations (perception of things that do not exist in reality)
Optic neuritis
Toxic optic neuropathy
Systemic lupus erythematosus (SLE), a disease affecting the immune system
Lazy eye (toxic amblyopia), increased blood urea nitrogen (a substance in the blood, whose increase may indicate kidney or liver dysfunction)
Increased levels of liver enzymes (substances in the blood, whose increase may indicate liver dysfunction)
Decreased hemoglobin (a substance that carries oxygen in the blood)
Decreased hematocrit (volume of blood occupied by red blood cells, a type of blood cell)
Reduced platelet aggregation activity (cells in the blood involved in the clotting process) and prolonged bleeding time
Decreased calcium levels in the blood

Very rare (affects less than 1 in 10,000 people):

Awareness of heartbeat (palpitations)
Reduced ability of the heart to pump blood through the body (heart failure)
Heart attack (myocardial infarction)
Fluid accumulation in the lungs (acute pulmonary edema)
Swelling due to fluid accumulation (edema)
Kidney disease (papillary necrosis)
High blood pressure (hypertension)
Disorders in red blood cell formation (with symptoms such as: fever, sore throat, mouth sores, flu-like symptoms, severe fatigue, nosebleeds and skin bleeding)
Ringing in the ears (tinnitus)
Esophagitis (inflammation of the esophagus, the tube that carries food to the stomach), pancreatitis (inflammation of the pancreas, a gland responsible for digesting certain substances and regulating blood sugar levels)
Intestinal narrowing (intestinal stenosis)
Acute liver inflammation (acute hepatitis)
Yellowing of the skin or whites of the eyes (jaundice)
Liver dysfunction or liver failure (reduced liver function)
Liver damage
Pancreatitis
Aseptic meningitis (inflammation without infection of the meninges, membranes covering the brain)
Flat, non-elevated reddish patches, target-shaped or circular rashes on the trunk, often with central blisters, 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)
Severe hypersensitivity reactions with swelling of the face, tongue, throat, narrowing of the airways, difficulty breathing (dyspnea), increased heart rate (tachycardia), decreased blood pressure leading to potentially life-threatening shock
Kidney damage. This effect is particularly likely if you/your child already have kidney, heart, or liver problems, are taking diuretic or ACE inhibitor medicines (See section “Other medicines and IBUPROFENE ZENTIVA ITALIA 200 mg”), or are elderly. This effect usually resolves upon discontinuation of treatment
Hair loss (alopecia)
Reduced number of: red blood cells (anemia), white blood cells (leucopenia), platelets (thrombocytopenia), all blood cells (pancytopenia). These conditions

may lead to fever, sore throat, mouth sores, flu-like symptoms, severe fatigue, nosebleeds, and skin bleeding
Not known (frequency cannot be estimated from available data):

Widespread, red, scaly rash with pustules under the skin and blisters mainly on skin folds, trunk, and upper limbs, accompanied by fever at the beginning of treatment (generalized exanthematous pustulosis). Stop using IBUPROFENE ZENTIVA ITALIA if you develop these symptoms and contact your doctor immediately. See also section 2.
Chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome

A severe skin reaction known as DRESS syndrome may also occur. Symptoms of DRESS include: skin rash, fever, swollen lymph nodes, and increased eosinophils (a type of white blood cell).

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, please contact your doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE IBUPROFENE ZENTIVA ITALIA 200 MG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after Exp. The expiry
date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. PACK CONTENTS AND OTHER INFORMATION

What IBUPROFENE ZENTIVA ITALIA 200 mg contains

The active substance is ibuprofen. Each film-coated tablet contains 200 mg of ibuprofen.
The other components are: Tablet core: microcrystalline cellulose, anhydrous colloidal silicon dioxide, hydroxypropylcellulose, sodium lauryl sulfate, sodium croscarmellose, talc. Film coating [Opadry (white) 06B28499]: hypromellose, macrogol 400, titanium dioxide (E171).

Description of the appearance of IBUPROFENE ZENTIVA ITALIA 200 mg and pack sizes
IBUPROFENE ZENTIVA ITALIA 200 mg is presented as white, oval, biconvex, film-coated tablets with a score line on one side. The tablets can be divided into two equal parts.
The tablets are packed in blisters, in cartons of 6, 12, or 24 tablets.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Zentiva Italia S.r.l., Via P. Paleocapa 7, 20121 Milano
Manufacturer
Balkanpharma – Dupnitsa AD - 3, Samokovsko Shose Str. - 2600 Dupnitsa (Bulgaria)
Balkanpharma – Razgrad AD - 68 Aprilsko vastanie Blvd - 7200 Razgrad (Bulgaria)

INSTRUCTIONS FOR USE: INFORMATION FOR THE USER

IBUPROFENE ZENTIVA ITALIA 400 mg film-coated tablets

Ibuprofen
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.
Always take this medicine exactly as described in this leaflet or as your doctor or
pharmacist has instructed you.

Keep this leaflet. You may need to read it again.
If you need more information or advice, consult your pharmacist.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Consult your doctor if you do not notice any improvement or if your symptoms worsen: after 3 days (in adolescents) or after 7 days (in adults) of treatment.

Contents of this leaflet:

What IBUPROFENE ZENTIVA ITALIA 400 mg is and what it is used for
What you need to know before taking IBUPROFENE ZENTIVA ITALIA 400 mg
How to take IBUPROFENE ZENTIVA ITALIA 400 mg
Possible side effects
How to store IBUPROFENE ZENTIVA ITALIA 400 mg
Contents of the pack and other information

1. WHAT IBUPROFEN ZENTIVA ITALIA 400 MG IS AND WHAT IT IS USED FOR

IBUPROFEN ZENTIVA ITALIA 400 mg contains ibuprofen, a medicine that belongs to a class of medicines called NSAIDs (non-steroidal anti-inflammatory drugs) which work by reducing pain, inflammation, and fever.
IBUPROFEN ZENTIVA ITALIA 400 mg is used in adults and adolescents aged 12 years and older to provide relief in the following conditions:

mild to moderate pain (such as headache, including migraine headache, toothache, and fever)
menstrual pain (dysmenorrhoea).

Consult a doctor if you do not feel better or if you feel worse after 3 days (in adolescents) or after 7 days (in adults).

2. WHAT YOU NEED TO KNOW BEFORE USING IBUPROFEN ZENTIVA ITALIA 400 MG

Do not use IBUPROFEN ZENTIVA ITALIA 400 mg

If you are allergic to ibuprofen or to any of the other ingredients of this medicine (listed in section 6)
If you are allergic to other non-steroidal anti-inflammatory drugs (NSAIDs)
If you have experienced allergic reactions such as asthma, excessive nasal discharge (rhinitis), itchy skin rash (urticaria), or swelling of the lips, face, tongue, or throat (angioedema) after taking medicines containing acetylsalicylic acid or other painkillers or anti-inflammatory drugs (NSAIDs)
If you have previously suffered from stomach or intestinal damage (ulcer) or bleeding related to the use of painkillers or anti-inflammatory drugs (NSAIDs)
If you currently have or have previously had stomach or intestinal ulcer or bleeding, or have experienced two or more such episodes in the past
If you currently suffer from or have previously suffered from ulcerative colitis, Crohn’s disease, peptic ulcer, or recurrent gastrointestinal bleeding (defined as two or more distinct episodes of confirmed ulceration or hemorrhage)
If you suffer from or have suffered from a congenital disorder affecting porphyrin metabolism (e.g., acute intermittent porphyria)
Chronic alcoholism (14 to 20 drinks/week or more)
If you suffer from severe liver (hepatic insufficiency), kidney (renal insufficiency), or heart (heart failure) problems, or have coronary artery disease (the blood vessels supplying the heart)
If you are in the last three months of pregnancy
If you are breastfeeding (see section “Fertility, pregnancy and breastfeeding”)
If you have significant fluid loss from the body (dehydration) due to vomiting, diarrhea, or insufficient fluid intake
If you have active bleeding (including in the brain)
If you suffer from an unknown-origin disease causing abnormal blood cell formation (dysmyelopoiesis)
If you are under 6 years of age

Warnings and precautions
Consult your doctor or pharmacist before taking IBUPROFEN ZENTIVA ITALIA 400 mg.
Anti-inflammatory/pain-relieving medicines such as ibuprofen may be associated with a modest
increase in the risk of heart attack or stroke, especially when administered at high doses. Do not
exceed the recommended dose or duration of treatment.
Signs of an allergic reaction to this medicine, including breathing difficulties, facial and neck swelling (angioedema), and chest pain, have been reported with ibuprofen.
Stop treatment with IBUPROFEN ZENTIVA ITALIA immediately and contact your doctor or emergency medical services immediately if you notice any of these signs.
You should discuss treatment with your doctor or pharmacist before taking IBUPROFEN ZENTIVA
ITALIA 400 mg if you:

Have heart problems, including heart attack, angina (chest pain), or a history of heart attack, coronary bypass surgery, peripheral arterial disease (poor circulation to legs or feet due to narrowed or blocked arteries), or any type of stroke (including “mini-stroke” or TIA, transient ischemic attack)
Have high blood pressure, diabetes, high cholesterol, a family history of heart disease or stroke, or if you are a smoker
Suffer from congestive heart failure
Suffer from an autoimmune disease called systemic lupus erythematosus (SLE) or other diseases affecting the immune system
Suffer from an inherited disorder affecting hemoglobin, a substance that carries oxygen in the blood (acute intermittent porphyria)
Are significantly dehydrated (due to vomiting, diarrhea, or insufficient fluid intake)
Suffer from chronic inflammatory bowel diseases such as intestinal inflammation with ulcers (ulcerative colitis), inflammation of the digestive tract (Crohn’s disease), or other stomach and intestinal disorders
Have previously suffered from a stomach or intestinal lesion (ulcer), particularly if complicated by perforation or accompanied by bleeding. Report any unusual stomach or intestinal symptoms (especially bleeding or ulceration) to your doctor immediately, particularly if they occur at the beginning of treatment. These symptoms are more likely if you are elderly. See section “Possible side effects”
Suffer from disorders of blood cell formation (hematopoietic disorder)
Suffer from disorders related to normal blood clotting mechanisms
Suffer from allergies, nasal mucosa disorders (hay fever), asthma, chronic nasal swelling (adenoids), or chronic obstructive respiratory diseases (asthma)
Suffer from liver, kidney, heart problems, or high blood pressure (especially if you are elderly)
Have recently undergone surgery
Are in the first six months of pregnancy
Are breastfeeding
Experience blurred vision or other eye symptoms, skin rash, weight gain, or fluid retention (edema)
Have an infection – see section “Infections” below

Respiratory disorders
Special precautions must be taken in patients with asthma or a history of asthma, bronchial diseases, chronic rhinitis, or respiratory diseases, as ibuprofen may trigger bronchospasm, urticaria, or angioedema in these patients.
Allergic reactions
Severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed, although rarely. At the first signs of a hypersensitivity reaction after taking Ibuprofen Zentiva Italia, treatment must be discontinued. Appropriate medical measures, depending on symptoms, should be initiated by specialized personnel. Caution is required in patients who have previously experienced allergic or hypersensitivity reactions to other substances, as they may have an increased risk of hypersensitivity reactions to ibuprofen. Caution is also required in patients with hay fever, nasal polyps, or chronic obstructive respiratory tract infections, as this increases the risk of allergic reactions. These may present as asthma attacks (so-called analgesic-induced asthma), Quincke’s edema, or urticaria.
Cardiac, renal, or hepatic disorders
Precautions are necessary in patients with renal, hepatic, or cardiac insufficiency, as NSAID use may worsen renal function. The habitual concurrent use of multiple painkillers further increases this risk. In these patients, the dose should be as low as possible and the treatment duration as short as possible (see section “Do not take Ibuprofen Zentiva Italia”).
Effects on kidneys
At the beginning of treatment, ibuprofen, like other NSAIDs, must be administered cautiously in patients with significant dehydration (risk of renal failure, especially in dehydrated children, adolescents, and elderly patients). As with other NSAIDs, prolonged administration of ibuprofen has caused papillary necrosis and other pathological renal changes. Cases of renal toxicity have occurred in patients where prostaglandins play a compensatory role in maintaining renal perfusion. In these patients, NSAID administration may cause dose-dependent reduction in prostaglandin formation and, consequently, in renal blood flow, potentially leading to overt renal failure. Most patients at risk for this reaction are those with renal dysfunction, heart failure, liver disease, those taking diuretics and ACE inhibitors, and elderly patients.
Discontinuation of NSAID therapy is generally followed by return to the pre-treatment condition.
Aseptic meningitis
Rarely, aseptic meningitis has been observed in patients treated with ibuprofen.
Although more likely in patients with systemic lupus erythematosus and connective tissue diseases, cases of aseptic meningitis have been reported in patients without underlying chronic conditions.
Hematological effects
Ibuprofen, like other NSAIDs, may inhibit platelet aggregation and prolong bleeding time in normal patients.
Exceptionally, chickenpox may lead to severe skin or soft tissue infections. To date, the role of NSAIDs in worsening these symptoms cannot be excluded. Therefore, it is recommended to avoid the use of Ibuprofen Zentiva Italia in case of chickenpox.
Elderly population
Elderly patients have a higher frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which can be fatal.
Gastrointestinal bleeding, ulceration, and perforation:
Ibuprofen should be administered with caution to patients with a history of peptic ulcer or other gastrointestinal disorders, as these conditions may be exacerbated. Cases of potentially fatal gastrointestinal bleeding, ulceration, and perforation have been reported with all NSAIDs at various stages of treatment, with or without warning symptoms or history of serious gastrointestinal events. The risk of bleeding, ulceration, or perforation is higher with higher ibuprofen doses, in patients with a history of peptic ulcer (especially if associated with bleeding or perforation), and in elderly patients. In these patients, treatment should be initiated with the lowest effective dose. Concomitant administration of protective agents (e.g., misoprostol or proton pump inhibitors) should be considered in these patients, as well as in those requiring concomitant low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk. Precautions should be taken in patients requiring concomitant use of other drugs that may increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid. If gastrointestinal bleeding or ulceration occurs in patients taking Ibuprofen Zentiva Italia, treatment must be discontinued. Concomitant administration of Ibuprofen Zentiva Italia with other NSAIDs, including selective COX-2 inhibitors, must be avoided due to the increased risk of ulceration or hemorrhage. Patients with a history of gastrointestinal disorders, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) early in treatment.
Infections
Ibuprofen Zentiva Italia may mask symptoms of infections such as fever and pain. Therefore, Ibuprofen Zentiva Italia may delay appropriate treatment of infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Medicines such as IBUPROFEN ZENTIVA ITALIA 400 mg may be associated with a modest increase in the risk of thrombus formation (arteriovenous thrombotic events), such as heart attack (“myocardial infarction”) or stroke (lack of blood flow to the brain). This risk is more likely with high doses and prolonged treatment.
Ibuprofen may temporarily increase the tendency to bleed.
Skin reactions
Serious skin reactions have been reported in association with IBUPROFEN ZENTIVA ITALIA treatment, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and generalized acute exanthematous pustulosis (PEAG). Discontinue use of IBUPROFEN ZENTIVA ITALIA and contact your doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.
Adolescents
In dehydrated adolescents, there is a risk of impaired renal function.
Other medicines and IBUPROFEN ZENTIVA ITALIA 400 mg
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
IBUPROFEN ZENTIVA ITALIA 400 mg may affect or be affected by other medicines. For example:

Other NSAIDs and/or acetylsalicylic acid (used for pain and inflammation treatment) (e.g., COX-2 inhibitors or other NSAIDs). See section “Do not use IBUPROFEN ZENTIVA ITALIA 400 mg”
Corticosteroids, used to treat inflammation
Medicines with anticoagulant effects (i.e., substances that thin the blood to prevent clotting, e.g., aspirin/acetylsalicylic acid, warfarin, ticlopidine): NSAIDs may enhance the effects of anticoagulants such as warfarin. Acetylsalicylic acid: as with other NSAIDs, co-administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential increase in adverse effects.
Medicines that lower high blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, angiotensin II receptor antagonists such as losartan)
Other anticoagulant medicines, such as heparin and clopidogrel: increased risk of gastrointestinal bleeding with NSAIDs
Methotrexate: NSAIDs may reduce its elimination and consequently increase methotrexate plasma levels
Digoxin (used to treat various heart conditions)
Phenytoin (used to treat epilepsy)
Lithium: NSAIDs may reduce lithium elimination
Diuretics, including potassium-sparing diuretics, which increase urine production
Cholestyramine: concomitant administration of ibuprofen and cholestyramine may reduce ibuprofen absorption from the gastrointestinal tract. However, the clinical significance is unknown.
Antibiotics such as aminoglycosides: NSAIDs may reduce aminoglycoside elimination
Quinolone antibiotics: patients taking NSAIDs and quinolones may be at higher risk of developing seizures
SSRIs, medicines used to treat depression
Moclobemide (used to treat depressive illness or social phobia)
Cyclosporine: concomitant administration of NSAIDs and cyclosporine increases the risk of nephrotoxicity
Antihypertensives, beta-blockers, and diuretics: NSAIDs may reduce the effectiveness of these drugs. Diuretics may increase the risk of NSAID-induced nephrotoxicity. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with compromised renal function), concomitant administration of an ACE inhibitor, beta-blocker, or angiotensin II antagonist and agents inhibiting cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be used with caution, especially in the elderly. Patients should be adequately hydrated, and monitoring of renal function should be considered after initiation of concomitant therapy and periodically thereafter.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors:
Concomitant administration of Ibuprofen Zentiva Italia with other NSAIDs, including selective COX-2 inhibitors, must be avoided due to the potential additive effect. Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.
Tacrolimus: possible increased risk of nephrotoxicity when an NSAID is administered with tacrolimus
Zidovudine: increased risk of hematological toxicity when an NSAID is administered with zidovudine
Or ritonavir, used in the treatment of HIV patients
Ginkgo Biloba: may increase the risk of bleeding with NSAIDs
Mifepristone: NSAIDs may reduce the effects of mifepristone
Probenecid or sulfinpyrazone: medicines containing probenecid or sulfalpyrazone may delay ibuprofen elimination
Sulfonylureas: NSAIDs may enhance the effects of sulfonylurea drugs (rare cases of hypoglycemia have been reported in patients receiving sulfonylurea and ibuprofen concurrently)
Corticosteroids, used to treat inflammation
Bisphosphonates, used in the treatment of certain bone diseases (osteoporosis and Paget’s disease) and to reduce elevated calcium levels in the blood
Oxpentifylline/pentoxifylline (used to treat a circulatory disorder in arms or legs)
Baclofen, a muscle relaxant

Other medicines may also influence or be influenced by treatment with IBUPROFEN
ZENTIVA ITALIA 400 mg. Therefore, always consult your doctor or pharmacist before using
IBUPROFEN ZENTIVA ITALIA 400 mg with other medicines.
IBUPROFEN ZENTIVA ITALIA 400 mg with food, drinks, and alcohol
Avoid drinking alcohol, as it may increase the undesirable effects of IBUPROFEN ZENTIVA
ITALIA 400 mg, particularly those affecting the stomach, intestine, or brain. See section “Driving and use of machines”.
Fertility, pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take IBUPROFEN ZENTIVA ITALIA 400 mg during the last three months of pregnancy, as it may harm the fetus or cause problems during delivery. It may cause kidney and heart problems in the fetus. It may affect your and your baby’s tendency to bleed and delay or prolong labor.
You should not take IBUPROFEN ZENTIVA ITALIA during the first six months of pregnancy unless absolutely necessary and under medical advice.
If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible time should be used. From week 20 of pregnancy, IBUPROFEN ZENTIVA ITALIA may cause kidney problems in the fetus if taken for more than a few days, thereby reducing the levels of amniotic fluid surrounding the baby (oligohydramnios) or causing narrowing of a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is required for more than a few days, your doctor may recommend additional monitoring.
Breastfeeding
Ibuprofen passes into breast milk in very small amounts and generally does not require discontinuation of breastfeeding during short-term treatment. However, if prolonged treatment is prescribed, early weaning should be considered.
Fertility
This medicine belongs to a group of medicines (NSAIDs) that may impair fertility in women. This effect is reversible upon discontinuation of the medicine.
Driving and use of machines
Ibuprofen generally does not have undesirable effects on the ability to drive or use machinery. However, at high doses, undesirable effects such as fatigue, drowsiness, dizziness (reported as common), and visual disturbances (reported as uncommon) may occur, and in isolated cases, the ability to drive or use machinery may be impaired. The effect is enhanced by concomitant alcohol intake.
IBUPROFEN ZENTIVA ITALIA contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. HOW TO USE IBUPROFENE ZENTIVA ITALIA 400 MG

Use this medicine exactly as stated in this leaflet or as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.
If you have an infection, contact your doctor immediately if symptoms (e.g. fever and pain) persist or worsen (see section 2).
Undesirable effects can be minimized by using the lowest effective dose for the shortest time needed to control symptoms. Therefore, do not exceed the recommended dose or duration of treatment.

How much should you take?
The dose of ibuprofen depends on age and body weight.

Adults and adolescents over 12 years of age (≥ 40 kg):

Fever and mild to moderate pain: ½ - 1 tablet as a single dose or 3-4 times daily at intervals of 4-6 hours. The dosage for migraine headache is: 1 tablet as a single dose; if necessary, continue taking 1 tablet every 4-6 hours. The maximum daily dose must not exceed 3 tablets (1200 mg).
Menstrual pain (primary dysmenorrhea): ½ - 1 tablet 1-3 times daily at intervals of 4-6 hours, as needed. The maximum daily dose must not exceed 3 tablets (1200 mg).

Elderly
If you are elderly, you should always consult your doctor before using IBUPROFENE ZENTIVA ITALIA 400 mg, as you may be more susceptible to adverse effects, particularly gastrointestinal bleeding and perforation, which can be fatal. Your doctor will determine the appropriate dose for you.

If you have kidney or liver problems
If you have impaired kidney or liver function, always consult your doctor before taking IBUPROFENE ZENTIVA ITALIA 400 mg. Your doctor will determine your dose, the duration of treatment, and will monitor your kidney and liver function.

How to take this medicine

Swallow the tablets with a glass of water during or after meals.
The tablets may be swallowed whole or divided in half (divisible tablets) to facilitate swallowing or to adjust dosing.

For how long

This medicine is intended only for short-term treatment, not exceeding 7 days. If symptoms persist or worsen, consult your doctor.
If use of the medicine is required for more than 3 days in adolescents, or if symptoms worsen, you must consult a doctor.

If you take more IBUPROFENE ZENTIVA ITALIA 400 mg than you should
If you have taken more IBUPROFENE ZENTIVA than recommended, or if your child has accidentally taken this medicine, contact a doctor or the nearest hospital immediately for advice on potential risks and necessary actions.

Symptoms of overdose may include nausea, stomach pain, vomiting (possibly with blood), diarrhoea, headache, tinnitus, confusion, and uncontrolled eye movements.
At high doses, drowsiness, chest pain, palpitations, loss of consciousness, seizures (especially in children), weakness, dizziness, blood in the urine, low blood potassium levels, feeling cold, and breathing difficulties may occur.
Other possible symptoms include: agitation, disorientation, abdominal pain, deep sleep with reduced response to normal stimuli (lethargy), lowered body temperature (hypothermia), kidney problems, stomach and intestinal bleeding, profound loss of consciousness (coma), temporary cessation of breathing (apnea), diarrhoea, reduced activity of the nervous system and respiratory depression.
Additional symptoms may include: excitement, fainting, low blood pressure (hypotension), and decreased or increased heart rate (bradycardia or tachycardia).
If significantly high doses of ibuprofen are taken, severe kidney damage (renal failure) and liver damage may occur. In cases of severe poisoning, metabolic acidosis (increased acid levels in the blood) may develop.
Symptoms of overdose may appear within 4–6 hours after taking ibuprofen.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

If you forget to take IBUPROFENE ZENTIVA ITALIA 400 mg
If you forget to take a dose, take it as soon as possible, unless it is less than 4 hours before the next scheduled dose.
Do not take a double dose to make up for a missed dose.

If you stop taking IBUPROFENE ZENTIVA ITALIA 400 mg
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Infections and infestations
Exacerbation of inflammation related to skin infections (e.g., development of necrotizing fasciitis) may occur during use of NSAIDs. If signs of infection appear or worsen during ibuprofen use, patients should be advised to seek immediate medical attention.

Skin and subcutaneous tissue disorders
In rare cases, severe skin infections and soft tissue complications may occur during chickenpox infection (see also "Infections and infestations").

Cardiovascular and cerebrovascular effects
Clinical studies suggest that administration of ibuprofen, particularly at high doses (2400 mg daily) and during long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Warnings and precautions").

Gastrointestinal disorders
The most frequently observed adverse reactions are gastrointestinal in nature. Following administration of this medicine, nausea, dyspepsia, vomiting, haematemesis, flatulence, abdominal pain, diarrhoea, constipation, melena, aphthous stomatitis, gastrointestinal bleeding, and exacerbation of colitis or Crohn’s disease have been reported. Gastritis, gastric and duodenal ulcers, and gastrointestinal perforation have been observed less frequently.

Adverse reactions are more likely with higher doses and prolonged duration of treatment.

The following adverse reactions are listed according to their frequency of occurrence.

The following adverse reactions are serious and require immediate attention if they occur. STOP treatment with IBUPROFENE ZENTIVA ITALIA 400 mg and consult your doctor immediately if you experience any of the following symptoms:

Very common (may affect more than 1 in 10 people):

Disorders of the digestive tract such as heartburn (pyrosis), indigestion (dyspepsia), abdominal pain, nausea, vomiting, excessive gas in the stomach (flatulence), diarrhoea, constipation.

Common (may affect 1 to 10 in 100 people):

Inflammation of the intestine and worsening of inflammation of the colon (colitis) or of the digestive tract (Crohn’s disease)
Complications of diverticula—small pouches that form in the lower part of the intestine (perforation or fistula)
Stomach and intestinal lesions (gastrointestinal ulcers), sometimes with bleeding, which may lead to anaemia (reduction in haemoglobin in the blood—the substance that carries oxygen), melena (black stools), haematemis (blood in vomit), ulcerative stomatitis (inflammation of the mouth mucosa), colitis. These effects generally increase with higher doses of ibuprofen or if you are taking certain other medicines (see section “Other medicines and IBUPROFENE ZENTIVA ITALIA 400 mg”). Elderly patients are more susceptible to gastrointestinal bleeding and perforation. These effects may also be fatal.
Headache
Drowsiness
Dizziness
Vertigo
Fatigue
Restlessness
Insomnia
Irritability

Uncommon (may affect 1 to 10 in 1,000 people):

Inflammation of the stomach (gastritis)
Kidney problems (nephrotic syndrome), development of oedema (swelling due to fluid accumulation), leg swelling, inflammation of the kidneys (interstitial nephritis), reduced kidney function (renal failure)
Increased sensitivity of the skin to sunlight (photosensitivity)
Visual disturbances
Insomnia
Anxiety
Paresthesia
Hearing impairment
Excessive nasal discharge (rhinitis)
Breathing difficulties (bronchospasm), allergic reactions such as skin rashes (exanthema and urticaria), itching, skin redness due to capillary rupture (purpura), asthma attacks sometimes accompanied by low blood pressure (hypotension)

Rare (may affect 1 to 10 in 10,000 people):

Depression
Confusional state
Hallucinations (perception of things that do not exist in reality)
Optic neuritis
Toxic optic neuropathy
Systemic lupus erythematosus (SLE)—an autoimmune disease
Lazy eye (toxic amblyopia)
Increased blood urea nitrogen (a substance in the blood; elevated levels may indicate kidney or liver dysfunction)
Increased liver enzyme levels (substances in the blood; elevated levels may indicate liver dysfunction)
Decreased haemoglobin (a substance that carries oxygen in the blood)
Decreased haematocrit (volume of blood occupied by red blood cells, a type of blood cell)
Reduced platelet aggregation activity (blood cells involved in the clotting process) and prolonged bleeding time
Decreased blood calcium levels
Increased blood uric acid levels

Very rare (may affect less than 1 in 10,000 people):

Awareness of heartbeat (palpitations)
Reduced ability of the heart to pump blood (heart failure)
Heart attack (myocardial infarction)
Fluid accumulation in the lungs (acute pulmonary oedema)
Swelling due to fluid accumulation (oedema)
Kidney disease (papillary necrosis)
High blood pressure (hypertension)
Disorders in red blood cell formation (symptoms include: fever, sore throat, mouth sores, flu-like symptoms, severe fatigue, nosebleeds, skin bleeding)
Ringing in the ears (tinnitus)
Oesophagitis (inflammation of the oesophagus—the tube carrying food to the stomach), pancreatitis (inflammation of the pancreas—an organ involved in digestion and blood sugar regulation)
Intestinal narrowing (intestinal stenosis)
Acute liver inflammation (acute hepatitis)
Yellowing of the skin or whites of the eyes (jaundice)
Liver dysfunction or liver failure (reduced liver function)
Liver damage
Pancreatitis
Aseptic meningitis (inflammation of the meninges—membranes covering the brain—without infection)
Severe skin rash with blisters (erythema multiforme, exfoliative dermatitis)
Red, non-elevated skin lesions resembling targets or circles on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital, and eye ulcers. These severe skin reactions may be preceded by fever and flu-like symptoms (exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)
Severe hypersensitivity reactions with swelling of the face, tongue, or throat, narrowing of airways, difficulty breathing (dyspnoea), increased heart rate (tachycardia), reduced blood pressure leading to potentially life-threatening shock
Kidney damage. This effect is particularly likely if you/your child has pre-existing kidney, heart, or liver problems, is taking diuretics or ACE inhibitors (see section “Other medicines and IBUPROFENE ZENTIVA ITALIA 400 mg”), or is elderly. This effect usually resolves upon discontinuation of treatment
Hair loss (alopecia)
Decreased number of: red blood cells (anaemia), white blood cells (leucopenia), platelets (thrombocytopenia), or all blood cells (pancytopenia). These conditions may cause fever, sore throat, mouth ulcers, flu-like symptoms, severe fatigue, nosebleeds, and skin bleeding

Not known (frequency cannot be estimated from available data):

Widespread, red, scaly rash with pustules under the skin and blisters mainly appearing in skin folds, trunk, and upper limbs, accompanied by fever at the beginning of treatment (generalized pustular eruption—acute generalized exanthematous pustulosis, AGEP). Stop using IBUPROFENE ZENTIVA ITALIA immediately if you develop these symptoms and contact your doctor immediately. See also section 2.
Chest pain, which may be a sign of a potentially serious allergic reaction known as Kounis syndrome

A serious skin reaction known as DRESS syndrome may also occur. Symptoms of DRESS include: skin rash, fever, swollen lymph nodes, and increased eosinophils (a type of white blood cell).

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report adverse reactions directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE IBUPROFENE ZENTIVA ITALIA 400 MG

This medicine does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after Exp. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. PACK CONTENTS AND OTHER INFORMATION

What IBUPROFENE ZENTIVA ITALIA 400 mg contains

The active substance is ibuprofen. Each film-coated tablet contains 400 mg of ibuprofen.
The other components are: Tablet core: microcrystalline cellulose, anhydrous colloidal silica, hydroxypropylcellulose, sodium lauryl sulfate, sodium croscarmellose, talc. Film coating [Opadry (white) 06B28499]: hypromellose, macrogol 400, titanium dioxide (E171).

Description of the appearance of IBUPROFENE ZENTIVA ITALIA 400 mg and pack sizes
IBUPROFENE ZENTIVA ITALIA 400 mg is presented as white, oval, biconvex, film-coated tablets with a score line on one side. The tablets can be divided into two equal parts.
The tablets are packed in blisters in cardboard boxes containing 6 or 12 tablets.