Ibuprofen Zentiva 200mg Anti-inflammatory 24 Softgels

NAME
IBUPROFENE ZENTIVA SOFT CAPSULES

PHARMACOTHERAPEUTIC CATEGORY
Non-steroidal anti-inflammatory and antirheumatic drugs.

ACTIVE PRINCIPLES
Ibuprofen.

EXCIPIENTS
Macrogol 600; potassium hydroxide 85% (E525); jelly; purified water; liquid sorbitol, partially dehydrated (E420); carmine red 43% (E120).

INDICATIONS
Symptomatic treatment of headaches, migraines, dental pain, back pain, dysmenorrhea, muscle pain, neuralgia, minor arthritic conditions, rheumatic pain, colds accompanied by fever and flu; the 400 mg medicine is recommended for adults and adolescents over 12 years of age (body weight equal to or greater than 40 kg); given the quantity of active ingredient contained in a capsule, the drug 200 mg is recommended for adults and children over 6 years of age (body weight equal to or greater than 20 kg).

CONTRAINDICATIONS / SECONDARY EFFECT
Hypersensitivity to the active substance or to any of the listed excipients; patients with a history of hypersensitivity reactions' (eg bronchospasm, asthma, rhinitis, angioedema or urticaria) associated with the intake of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs (NSAIDs); presence or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of ulceration or bleeding demonstrated); history of gastrointestinal bleeding or perforation related to previous NSAID therapy; disorders of blood coagulation and hematopoiesis; patients with severe hepatic insufficiency, severe renal insufficiency or severe heart failure; during the last trimester of pregnancy there is a risk of premature closure of the fetal arterial duct, with possible persistent pulmonary hypertension. Labor can be delayed and last longer, with a greater tendency to bleeding for both mother and baby. The drug 200 mg is not suitable for children younger than 6 years (body weight <20 kg), due to the quantity of active ingredient contained in one capsule. The 400 mg medicine is not suitable for children under 12 years of age (body weight <40kg), due to the quantity of active ingredient contained in a capsule.

DOSAGE
For oral administration and short-term use only. Adults and adolescents over 12 years of age (body weight of 40 kg or more): the lowest effective dose should be used for the minimum time necessary to relieve symptoms. Adults should seek medical attention if symptoms persist or worsen, or if the product is needed for more than 10 days. Consult your doctor if in adolescents (older than 12 years) the medicine is needed for more than 3 days or if symptoms worsen. The recommended dose ranges from 200 mg to 400 mg of ibuprofen, up to three times a day as needed. The interval between two doses should be at least 4 hours. Do not exceed the dose of 1200 mg in 24 hours. Children over 6 years of age (body weight <= 39 kg): the product containing 200 mg of ibuprofen is recommended for children aged between 6 and 12 years. Ibuprofen 200 mg should only be used in children weighing at least 20 kg. The maximum total daily dose of ibuprofen is 20-30 mg per kg of body weight, divided into 3-4 single doses, at dose intervals of 6-8 hours. Do not exceed the maximum recommended daily dose. Do not exceed the total dose of 30 mg / kg of ibuprofen in 24 hours. In children, the following administration instructions apply for ibuprofen 200 mg. Children from 20 to 29 kg: 1 capsule of ibuprofen 200 mg (ibuprofen 200 mg); maximum daily dose in number of capsules 3 (equivalent to 600 mg of ibuprofen). Children from 30 to 39 kg: 1 capsule of ibuprofen 200 mg (ibuprofen 200mg); maximum daily dose in number of capsules 4 (equivalent to 800 mg of ibuprofen). Children under 6 years of age (body weight <20 kg): ibuprofen 200 mg and 400 mg are not suitable for children under 6 years of age (body weight <20 kg), due to the amount of active ingredient contained in a capsule. Elderly The dosage for the elderly is the same as for adults, but more caution should be exercised. Patients with hepatic or renal impairment: No dose reduction is required in patients with renal or mild to moderate hepatic impairment, however more caution should be exercised. Method of administration: The capsules should be swallowed whole with a sufficient amount of liquid. The capsule can be taken with or without meals. Intake during meals or immediately after meals may delay the onset of action. However, taking it with meals improves the tolerability of the product and reduces the likelihood of gastrointestinal problems.

STORAGE
Store below 25 degrees C. Store in the original package to protect from moisture.

WARNINGS
Undesirable effects can be limited by using the lowest effective dose for the minimum duration necessary to control symptoms (see gastrointestinal (GI) and cardiovascular risk below). There is a risk of renal damage in dehydrated children and adolescents. The elderly have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal. Bronchospasm may worsen in patients with bronchial asthma or allergic disease or with a history of these disorders. Caution should be exercised in patients suffering from allergic rhinitis, nasal polyps or chronic obstructive respiratory disorders, as there is a greater risk of allergic reactions in these patients. Concomitant use of ibuprofen and other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. Systemic lupus erythematosus and mixed connective tissue disease increase the risk of aseptic meningitis. There is a risk of kidney damage as kidney function may deteriorate further. Monitoring of renal function is recommended in patients at risk, e.g. patients with heart and renal insufficiency, patients treated with diuretics or in case of dehydration of any aetiology. In general, the habitual intake of analgesics, in particular the combination of various active ingredients to relieve pain, can cause permanent renal damage, with the risk of renal failure (analgesic nephropathy). The risk may increase in case of physical stress associated with salt loss and dehydration. Therefore, it must be avoided. Hepatic dysfunction. In case of prolonged administration, control of blood counts and regular monitoring of renal and hepatic function are advisable. Treatment with ibuprofen should be discontinued in case of deterioration of liver function related to its administration. The state of health usually returns to normal after stopping treatment. Occasional blood glucose monitoring is also advisable. Caution is required before initiating treatment in patients with a history of hypertension and / or heart failure, as fluid retention, hypertension and edema have been reported in association with NSAID therapy. Data from clinical and epidemiological studies suggest that the use of ibuprofen, particularly at high doses (2400 mg per day) and in the case of long-term treatment, may be associated with a slightly increased risk of arterial thrombotic events. In general, epidemiological studies do not suggest that low doses of ibuprofen (e.g. <= 1200 mg per day) are associated with an increased risk of myocardial infarction. Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ibuprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease. There is evidence that drugs that inhibit cyclo-oxygenase / prostaglandin synthesis may impair female fertility through an effect on ovulation. This effect is reversible after discontinuation of treatment. In women who have difficulty conceiving or who are undergoing an assessment of their fertility, discontinuation of ibuprofen therapy should be considered. NSAIDs should be administered with caution to patients with a history of gastrointestinal disease, as these disorders may be exacerbated. Life-threatening gastrointestinal (GI) bleeding, ulceration or perforation have been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of GI events. With increasing NSAID doses, the risk of gastrointestinal (GI) bleeding, ulceration or perforation is greater in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should start treatment at the lowest available dose. For these patients, as well as for patients requiring the concomitant use of low doses of acetylsalicylic acid or other active substances that may increase gastrointestinal risk, combined therapy with protective agents should be considered. Patients with a history of gastrointestinal (GI) toxicity, particularly the elderly, should report any unusual abdominal symptoms, particularly during the initial stages of treatment. Caution is advised in patients receiving concomitant medications that may increase the risk of gastrointestinal (GI) ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid. If gastrointestinal (GI) bleeding or ulceration occurs in patients taking ibuprofen, treatment should be stopped. Serious skin reactions, some fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at a higher risk of developing these reactions at the start of therapy: in the majority of cases, the reactions occur within the first month of treatment. Ibuprofen therapy should be discontinued as soon as skin rashes, mucosal lesions or any other signs of hypersensitivity appear. Other notes Prolonged use of any type of pain reliever for headache can worsen the disorder. If this occurs or is suspected, discontinue treatment. A diagnosis of drug overuse headache should be suspected in patients with frequent or daily headaches despite (or as a consequence of) regular use of headache medications. As a consequence of the concomitant consumption of alcohol, the undesirable effects of the active substance, in particular those concerning the gastrointestinal tract or the central nervous system, could be increased during the use of NSAIDs. Ibuprofen can mask the symptoms of an infection (fever, pain and swelling). The drug contains sorbitol. Ibuprofen 200 mg contains 16 mg of potassium per capsule. Ibuprofen 400mg contains 32mg of potassium per capsule.

INTERACTIONS
Concomitant use with other NSAIDs, including specific cyclooxygenase-2 inhibitors, increases the risk of adverse reactions. Ibuprofen (like other NSAIDs) should not be used in combination with: Aspirin: except in the case of low dose aspirin (not exceeding 75 mg per day) prescribed by a doctor, because it could increase the risk of adverse reactions. Experimental data suggest that, taken concomitantly, ibuprofen may inhibit the effect of low-dose aspirin on platelet aggregation. However, the limitations of these data and the uncertainty regarding the extrapolation of the ex vivo data of the situation in clinical practice do not allow definitive conclusions to be drawn for the regular use of ibuprofen, furthermore, clinically relevant effects in case of occasional use are not considered likely. of ibuprofen. Other NSAIDs including selective cyclooxygenase-2 inhibitors: Avoid concomitant use of two or more NSAIDs, as it may increase the risk of adverse reactions. Ibuprofen should be used with caution in combination with: Corticosteroids: because they may increase the risk of gastrointestinal ulceration or bleeding. Antihypertensives and diuretics: because NSAIDs can reduce the effect of these drugs. Diuretics may increase the risk of NSAID nephrotoxicity. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with renal impairment) coadministration of an ACE inhibitor, beta receptor blockers or angiotensin II antagonists and cyclooxygenase inhibiting agents may result in further deterioration renal function, including possible acute renal failure, usually reversible. Therefore, this combination should be administered 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. Potassium-sparing diuretics: concomitant administration of ibuprofen and potassium-sparing diuretics may cause hyperkalaemia (monitoring of serum potassium is recommended). Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin. Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): can increase the risk of gastrointestinal bleeding. Cardiac glycosides: NSAIDs can exacerbate heart failure, decrease glomerular filtration rate (GFR) and increase Plasma levels of diglycosides Lithium: There is evidence of a possible increase in plasma levels of lithium Methotrexate: There is evidence of a possible increase in plasma levels of methotrexate and an increase in its toxic effect, in particular its haematological toxic effects Baclofen: vi there are clinical data that indicate that NSAIDs may increase the plasma level of this drug. Ciclosporin: increased risk of nephrotoxicity. Mifepristone: NSAIDs should not be used for 8-12 days after administration of mifepristone, as they may reduce its effect Tacrolimus: Possible increased risk of nephrotos safety when NSAIDs are administered with tacrolimus. Zidovudine: increased risk of haematological toxicity if NSAIDs are administered concomitantly with zidovudine. There is evidence of an increased risk of haemarthrosis and hematoma in HIV positive haemophiliacs receiving concomitant treatment with zidovudine and ibuprofen. Quinolone antibiotics: Data from animal studies indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may be at an increased risk of developing seizures. Sulfonylurea derivatives: Clinical trials have indicated interactions between non-steroidal anti-inflammatory drugs and antidiabetic drugs (sulfonylureas). Although no interactions between ibuprofen and sulfonylureas have been described so far, a precautionary check of blood glucose values is recommended in case of concomitant intake. Sulfinpyrazone, probenecid: Medicines containing probenecid or sulfinpyrazone may delay the excretion of ibuprofen. Aminoglycosides: Since ibuprofen may decrease the clearance of aminoglycosides, co-administration may increase the risk of nephrotoxicity and toxicity. Pemetrexed: concomitant administration may increase the toxic effects of pemetrexed.

SIDE EFFECTS
Hypersensitivity reactions have been reported, which may consist of non-specific allergic reactions and anaphylaxis; respiratory tract reactivity, for example, asthma, aggravated asthma, bronchospasm, dyspnoea; various skin reactions, for example itching, urticaria, angioedema and, more rarely, exfoliative and bullous dermatitis (including epidermal necrolysis and erythema multiforme). The following list of adverse effects related to those seen with ibuprofen at over-the-counter doses for short-term use. Additional adverse effects may occur in the treatment of chronic conditions or in long-term treatment. Disorders of the blood and lymphatic system. Very rare: haematopoietic disorders (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, bleeding and bruising of unknown origin. Disorders of the immune system. Very rare: isolated cases of aseptic meningitis symptoms such as neck stiffness, headache, nausea, vomiting, fever or disorientation have been observed in patients with pre-existing autoimmune diseases (such as systemic lupus erythematosus, mixed connective tissue disease). Nervous system disorders: Uncommon: headache; very rare: aseptic meningitis, isolated cases have been reported. Ear and labyrinth disorders. Not known: hearing impairment. Gastrointestinal disorders. Uncommon: abdominal pain, dyspepsia and nausea; Rare: diarrhea, flatulence, constipation, vomiting; Very rare: peptic ulcer, gastrointestinal perforation or haemorrhage, melaena, haematemesis, sometimes fatal, particularly in the elderly, ulcerative stomatitis, gastritis. exacerbation of ulcerative colitis and Crohn's disease. Hepatobiliary disorders. Very rare: liver disorders. Skin and subcutaneous tissue disorders. Uncommon: various skin rashes; very rare: severe skin reactions such as bullous reactions may occur, including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis. Renal and urinary disorders. Very rare: acute renal failure, papillary necrosis, especially with long-term use, associated with increased serum urea and edema. Hypersensitivity reactions. Uncommon: hypersensitivity reactions' with urticaria and pruritus; very rare: severe hypersensitivity reactions. symptoms may include swelling of the face, tongue and larynx, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock), exacerbation of asthma and bronchospasm. Cardiovascular and cerebrovascular disorders: Edema, hypertension and heart failure have been reported in association with NSAID treatment. Clinical and epidemiological data suggest that the use of ibuprofen (particularly at high doses of 2400 mg per day) and in long-term treatment may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) . The reporting of suspected adverse reactions that occur after the authorization of the drug is important, as it allows continuous monitoring of the benefit / risk ratio of the drug.

PREGNANCY AND BREASTFEEDING
Inhibition of prostaglandin synthesis can have negative effects on pregnancy and / or embryo-fetal development. Data from epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The risk was believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss and embryo-fetal mortality. Furthermore, an increased incidence of various malformations, including cardiovascular, has been reported in animals administered prostaglandin synthesis inhibitors during the organogenetic period. Ibuprofen should not be given during the first and second trimester of pregnancy unless clearly necessary. If ibuprofen is used by women who are attempting to conceive, or during the first or second trimester of pregnancy, the dose should be kept as low as possible and the duration of treatment should be as short as possible. In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to: cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension); renal dysfunction, which can progress to renal failure with oligohydroamnios; the mother and the newborn, at the end of pregnancy, to: a possible prolongation of the bleeding time, an antiplatelet effect which could occur even at very low doses; an inhibition of uterine contractions, resulting in delayed or prolonged labor. Consequently, ibuprofen is contraindicated during the third trimester of pregnancy. In limited studies, ibuprofen has been found in breast milk at a very low concentration and is unlikely to have adverse effects on the nursing infant. There is some evidence that drugs that inhibit cyclooxygenase / prostaglandin synthesis may impair female fertility by having an effect on ovulation. This effect is reversible after discontinuation of treatment.