IBUPROFENE ZEN 20CPS MOL 400MG

IBUPROFECT ZENTIVA CAPSULE MOLLS

active ingredients

Each soft capsule contains ibuprofen 200 mg. Each soft capsule contains ibuprofen 400 mg. Excipient(s) with known effects: sorbitol (E420). IBUPROFECT ZENTIVA 200 mg contains 58.1 mg of sorbitol per capsule. IBUPROFECT ZENTIVA 400 mg contains 100.7 mg of sorbitol per capsule. For the full list of excipients, see paragraph 6.1.

Excellent

Macrogol 600 Hydroxide Potassium 85% (E525) Gelatin Purified Water Liquid Sorbitol, partially dehydrated (E420) Red Carmine 43% (E120)

Therapeutic indications

IBUPROFECT ZENTIVA is indicated for the symptomatic treatment of cephales, migraine, dental pain, back pain, dysmenorrhea, muscle pain, neuralgia, non-gravious arthritic conditions, rheumatic pain, colds accompanied by fever and influence. IBUPROFECT ZENTIVA 400 mg is recommended for adults and adolescents aged 12 years (body weight equal to or greater than 40 kg). Given the amount of active ingredient contained in a capsule, IBUPROFENE ZENTIVA 200 mg is recommended for adults and children older than 6 years (body weight equal to or greater than 20 kg).

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients listed in paragraph 6.1; • Patients with a history of hypersensitivity reactions (e.g. bronchospasm, asthma, rhinitis, angioedema or urticaria) associated with the intake of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs (NSAID); • Presence or anamnes of peptic ulceration/recurrent bleeding (two or more distinct episodes of ulceration); • Anamnesis of bleeding or gastrointestinal perforation related to previous NSAID therapy; • Hemocoagulation and hemopoiesis disorders; • Patients with severe liver failure, severe kidney failure or severe heart failure (NYHA class IV). See also paragraph 4.4; • During the last trimester of pregnancy there is the risk of premature closure of fetal arterial duct, with possible persistent pulmonary hypertension. The labor can be delayed and lasting longer, with a greater tendency to bleeding both for the mother and for the child (see paragraph 4.6). IBUPROFECT ZENTIVA 200 mg is not suitable for children under the age of 6 (body weight

Population

Population Exclusively for oral administration and short term use. Adults and adolescents older than 12 years old (body weight equal to or greater than 40 kg) The minimum effective dose must be used for the minimum time necessary to relieve symptoms. Adults should contact the doctor if symptoms persist or worsen, or if the product is needed for more than 10 days. Consult your doctor if in adolescents (aged over 12 years) the medication is necessary for more than 3 days or if symptoms worsen. The recommended dose varies from 200 mg to 400 mg of ibuprofen, up to three times a day as needed. The interval between two doses must be at least 4 hours. Do not exceed 1200 mg dose in 24 hours. Children older than 6 years (body weight ≤ 39 kg) For children aged between 6 and 12 years, the product containing 200 mg of ibuprofen is recommended. IBUPROFECT ZENTIVA 200 mg should only be used in children weighing at least 20 kg. The maximum daily dose of ibuprofen is 20-30 mg per kg body weight, divided into 3-4 single doses, at dose intervals of 6-8 hours. Do not exceed the recommended maximum daily dose. Do not exceed the total dose of 30 mg/kg of ibuprofen in 24 hours. In children, for IBUPROFENE ZENTIVA 200 mg are the following administration instructions:

Body weight	Single dose in number of capsules	Maximum daily dose in capsule number
Children from 20 to 29 kg	1 capsule of IBUPROFENE ZENTIVA 200 mg (ibuprofen 200 mg)	3 (equivalent to 600 mg of ibuprofen)
Children from 30 to 39 kg	1 capsule of IBUPROFENE ZENTIVA 200 mg (ibuprofen 200 mg)	4 (equivalent to 800 mg of ibuprofen)

Consult your doctor if in children older than 6 years the medicine is necessary for more than 3 days or if symptoms worsen. Children under the age of 6 (body weight IBUPROFENE ZENTIVA 200 mg and IBUPROFENE ZENTIVA 400 mg are not suitable for children under the age of 6 (elderly body weight) The dosage for the elderly is the same as for adults, but it is necessary to provide greater caution (see paragraph 4.4). Hepatic insufficiency or kidney damage In patients with mild to moderate kidney damage or hepatic impairment, a dose reduction is not required, however, greater caution is required (see paragraph 4.4). Method of administration The capsules must be ingested whole with a sufficient amount of liquid. The capsule can be taken during or away from meals. Intake during meals or immediately after meals can delay the start of the action. However, taking during meals improves product tolerance and reduces the likelihood of gastrointestinal problems. Undesirable effects can be reduced by using the lowest effective dose for the shortest period necessary to control symptoms (see paragraph 4.4).

Conservation

Store at a temperature below 25°C. Store in the original packaging to protect the medicine from moisture.

Warnings

Undesirable effects can be limited using the minimum effective dose for the minimum duration needed to control symptoms (see gastrointestinal risk (GI) and cardiovascular risk below). Pediatric population There is a risk of kidney damage in dehydrated children and adolescents. Seniors The elderly have an increased frequency of adverse reactions to the NSAIDs, in particular bleeding and gastrointestinal perforations, which can be fatal (see paragraph 4.8). Respiratory effects In patients with bronchial asthma or allergic disease or with an amnesia of these disorders may worsen bronchospasm. Preserve caution in patients suffering from allergic rhinitis, nasal polyps or chronic obstructive respiratory disorders, because in these patients there is a greater risk of allergic reactions. Other Concurrent use of ibuprofen and other NSAIDs, including selective cyclooxygenase-2 inhibitors, must be avoided (see paragraph 4.5). Systemic erythematous lupus and mixed connectivity Systemic lupus erythematosum and mixed connectivity increasing the risk of aseptic meningitis (see paragraph 4.8). Renal effects There is a risk of kidney damage because the kidney function can worsen further (see paragraphs 4.3 and 4.8). Monitoring of kidney function is recommended in patients at risk, such as patients with heart and kidney failure, patients treated with diuretics or in case of dehydration of any etiology. In general, the usual intake of analgesics, in particular the combination of various active ingredients to relieve pain, can determine permanent kidney damage, with risk of kidney failure (nephropathy from analgesics). The risk can increase in case of physical stress associated with loss of salts and dehydration. Therefore, it must be avoided. Hepatitis effects Hepatic dysfunction (see paragraphs 4.3 and 4.8). In case of prolonged administration, control of the blood count and regular monitoring of the kidney and liver function are recommended. It is appropriate to stop therapy with ibuprofen in case of deterioration of the liver function related to its administration. Usually, after the interruption of treatment the state of health normalizes. Occasional blood glucose monitoring is also appropriate. Cardiovascular and cerebrovascular effects Precaution is necessary (also discussing with your doctor or pharmacist) before starting treatment in patients with an anamnesi of hypertension and/or heart failure, since in association with NSAID therapy water retention, hypertension and edema were reported. Clinical studies suggest that the use of ibuprofen, particularly at high doses (2400 mg/day) may be associated with a slight increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). In general, epidemiological studies do not suggest that a low dose of ibuprofen (e.g. ≤ 1200 mg/day) is associated with increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), proven ischemic cardiopathy, peripheral arteriopathy and/or cerebrovascular disease should be treated with ibuprofen only after careful evaluation and should be avoided high doses (2400 mg/day). In addition, careful consideration must be made before starting long-term treatments of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen are required (2400 mg/day). Comprogation of female fertility There are evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis can affect female fertility by an effect on ovulation. This effect is reversible after termination of treatment. In women who have difficulty in conceiving or who are evaluating their fertility, the suspension of treatment with ibuprofen should be assessed. Gastrointestinal effects (GI) NSAIDs should be administered with caution in patients with a gastrointestinal disease anamnesi ( ulcerative colitis, Crohn's disease), because these disorders can be exacerbated (see paragraph 4.8). Blood, ulceration or gastrointestinal perforations (GI) potentially fatal have been reported with all NSAIDs at any time during treatment, with or without premonitory symptoms or an earlier history of GI events. Upon increasing doses of NSAIDs, the risk of bleeding, ulceration or gastrointestinal perforation (GI) is greater in patients with an amnesia of ulcer, in particular if complicated by hemorrhage or perforation (see paragraph 4.3), and in the elderly. These patients must begin treatment at the minimum dose available. For these patients, as well as for patients requiring the concomitant use of low doses of acetylsalicylic acid or other active ingredients that may increase gastrointestinal risk (see below and paragraph 4.5), the combined therapy with protective agents (e.g. misoprostol or protonic pump inhibitors). Patients with a gastrointestinal toxicity analogy (GI), especially the elderly, must report any unusual abdominal symptoms (especially gastrointestinal bleeding (GI)), especially during the initial stages of treatment. It is recommended to provide caution in patients receiving concomitant medications that could increase the risk of gastrointestinal ulceration or bleeding (GI), such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplastrine agents such as acetyl acid (see paragraph 4.5). If a gastrointestinal bleeding or ulceration occurs (GI) in patients taking ibuprofen, treatment must be stopped. Dermatory effects Very rarely, in association with the use of NSAIDs serious skin reactions were reported, some fatal, including exfoliatory dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (see paragraph 4.8). Patients seem to be at the highest risk of developing these reactions at the beginning of therapy: in most cases reactions arise within the first month of treatment. Hybuprofen therapy should be interrupted as soon as skin rashes appear, mucosa lesions or any other sign of hypersensitivity. Other notes Prolonged use of any type of analgesic for cephalea can worsen the disorder. If you happen or suspect this situation, contact your doctor and stop treatment. You should suspect a diagnosis of headache from excessive use of drugs in patients with frequent or daily headaches despite (or as a result) regular use of headache medications. As a result of the concomitant consumption of alcohol, the undesirable effects of the active ingredient, particularly 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). Excipient IBUPROFECT ZENTIVA 200 mg contains 58.1 mg of sorbitol per capsule. IBUPROFECT ZENTIVA 400 mg contains 100.7 mg of sorbitol per capsule. Patients with hereditary fructose intolerance (HFI) should not be given this medicine. IBUPROFECT ZENTIVA 200 mg contains 16 mg potassium per capsule. IBUPROFECT ZENTIVA 400 mg contains 32 mg potassium per capsule.

Interactions

Concurrent use with other NSAIDs, including specific cyclooxygenase-2 inhibitors, increases the risk of adverse reactions. Hybuprofen (analogously to other NSAIDs) should not be used in association with: • Acetylsalicylic acid: the simultaneous administration of ibuprofen and acetylsalicylic acid is not generally recommended due to the potential increase in unwanted effects. Experimental data suggests that, taken at the same time, ibuprofen can competitively inhibit the effect of acetylsalicylic acid at low dosage on platelet aggregation. Although there are uncertainties regarding the extrapolation of these data to the clinical situation, the possibility that regular long-term use of ibuprofen can reduce the cardioprotective effect of acetylsalicylic acid at low dosage cannot be excluded. Clinically relevant effects are not considered likely in case of occasional use of ibuprofen (see paragraph 5.1). • Other NSAIDs included selective cyclooxygenase-2 inhibitors: Avoid the concomitant use of two or more NSAIDs, because it could increase the risk of adverse reactions (see paragraph 4.4). Hybuprofen should be used with caution in association with: • Corticosteroids: because they can increase the risk of gastrointestinal ulceration or bleeding (see paragraph 4.4). • Antihypertensives and diuretics: because NSAIDs can reduce the effect of such drugs. In some patients with impaired kidney function (e.g. dehydrated patients or elderly patients with kidney damage) the co-administration of an inhibitor ACE, beta receptor blockers or antagonists of angiotensin II and agents that inhibit cyclooxygenase can cause further deterioration of kidney function, including a possible acute kidney failure, usually reversible. Therefore, this combination must be given with caution, especially in the elderly. Patients should be properly hydrated and should be considered to monitor the kidney function after the start of the concomitant therapy and subsequently periodically. Diuretics can increase the risk of NSAID nephrotoxicity. • Diuretic potassium savers: Concurrent administration of ibuprofen and potassium-saving diuretics can cause hyperpotassiemia (short potassium control is recommended). • Antiagulants: NSAIDs can increase the effects of anticoagulants, such as warfarin (see paragraph 4.4). • Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): They can increase the risk of gastrointestinal bleeding (see paragraph 4.4). • Heart glycosides: NSAIDs can exacerbate heart failure, decrease glomerular filtration speed (GFR) and increase plasma levels of glycosides. • Litio: There are evidence of a possible increase in plasma levels of lithium. • Metotress: There are evidence of a possible increase in plasma levels of methorate and an increase in its toxic effect, in particular hematologic toxic effects. • Baclofene: clinical data indicate that NSAIDs can increase the plasma level of this drug. • Ciclosporin: Increased risk of nephrotoxicity. • Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration, as they can reduce its effect. • Tacrolimus: Possible increase in the risk of nephrotoxicity when NSAIDs are administered with tacrolimus. • Zidovudina: Increased risk of hematological toxicity if NSAIDs are administered simultaneously with zidovudine. There are evidence of a greater risk of hematoma and hematoma in positive HIV hemophiliacs that receive concomitant treatment with zidovudine and ibuprofen. • Chinolonic Antibiotics: Animal studies indicate that NSAIDs can increase the risk of convulsions associated with chinolonic antibiotics. Patients taking NSAIDs and kinolones can present a greater risk of developing seizures. • Derivati di sulfanilurea: clinical trials have indicated interactions between non-steroidal anti-inflammatory drugs and anti-diabetics (sulfaniluree). Although interactions between ibuprofen and sulfaniluree have not yet been described, a precautionary check of blood glucose values is recommended for concurrent intake. • Sulfinpirazone, probenecid: Drugs containing probenecid or sulfinpirazone may delay the excretion of ibuprofene. • Aminoglycosides: since ibuprofen may decrease clearance of aminoglycosides, co-administration may increase the risk of nephrotoxicity and ototoxicity. • Pemetrexed: concurrent administration can increase the toxic effects of pemetrexed.

Effects

The following table summarizes adverse reactions to the drug of ibuprofen divided into groups according to the MedDRA terminology together with their frequency: very common (≥1 / 10); common (≥1 / 100 a Classification for systems and organs according to MedDRA Frequency Undesirable effect Emolinfopoietic system pathologies Very rare Hematopoietic disorders (anemia, leucopenia, thrombocytopenia, pancitopenia, agranulocytosis). The first signs are: fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, severe fatigue, bleeding and ecchimosis of unknown origin. Immune system disorders Hypersensitivity reactions1 which consist of: Not common Hives, itching. Very rare Severe reactions of hypersensitivity. The symptoms may be: swelling of the face, tongue and larynx, dispnea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock). Notable Reactivity of the respiratory tract that includes asthma, aggravated asthma, bronchospasm or dispnea. Diseases of the nervous system Not common Cephalea. Very rare Synthetic Meningitis2. Ear and labyrinth pathologies Notable Compromise of hearing. Heart disease Notable Heart failure and edema. Vascular diseases Notable Hypertension. Gastrointestinal diseases Not common Abdominal pain, dyspepsia and nausea. Rare Diarrhea, flatulence, constipation and vomiting. Very rare Peptic ulcer, perforation or gastrointestinal hemorrhage, melena, ematemesis, sometimes fatal, especially in the elderly. (see paragraph 4.4). Ulcerative stomatitis, gastritis. Notable Exacerbation of ulcerative colitis and Crohn's disease (see paragraph 4.4). Hepatobiliary diseases Very rare Hepatic disorders. Pathologies of skin and subcutaneous tissue Not common Various rashes. Very rare Severe forms of skin reactions can occur, such as bollose reactions, including Stevens-Johnson syndrome, multiform erythema and toxic epidermal necrolysis. Notable Reaction from drug with eosinophilia and systemic symptoms ( DRESS syndrome), photosensitivity reaction. Kidney and urinary pathologies Very rare Acute renal insufficiency, papillary necrosis, especially in case of long-term use, associated with increased serum edema and edema. Notable Renal failure. Diagnostic examinations Very rare Reduction of hemoglobin levels. Clinical studies suggest that the use of ibuprofen (especially at high doses of 2400 mg/day) may be associated with a slight increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see paragraph 4.4). 1 hypersensitivity reactions have been reported, which may consist of a) non-specific allergic reactions and anaphylaxis; b) reactivity of the respiratory tract, for example, asthma, asthma aggravated, bronchospasm, dispnea; c) assorted skin disorders, including skin rashes of various types, such as itching, urticaria, purple, angioedema, and more rarely exfoliative and bollose dermatitis (including epidermal necrolysis and multiform erythema). 2 The pathogenic mechanism of aseptic meningitis induced by drugs is not fully understood. However, the available data on aseptic meningitis induced by NSAID leads to a reaction of hypersensitivity (due to a temporal relationship with the intake of the medicinal product, and the disappearance of symptoms after the suspension of the medicinal product). To be noted, individual cases of symptoms of aseptic meningitis (such as torcicollo, headache, nausea, vomiting, fever and disorientation) were observed during treatment with ibuprofen, in patients with existing autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease). Reporting of suspicious adverse reactions The reporting of suspicious adverse reactions that occur after the authorization of the medicinal product is important, as it allows continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare workers are required to report any suspected adverse reaction via the national reporting system at the address www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

Overdosing

In children ingestion of more than 400 mg/kg can cause symptoms. In adults the dose-response effect is less clear. The half-life in overdose is 1.5-3 hours. Synonyms Most patients who have ingested clinically important amounts of NSAID develops only nausea, vomiting, epigastric pain or, more rarely, diarrhea. Tinnitus, headache and gastrointestinal bleeding are also possible. In case of more severe poisoning, it is observed toxicity of the central nervous system that manifests itself as drowsiness and occasionally as excitement and disorientation or coma. Sometimes patients develop seizures. In case of severe poisoning it is possible that metabolic acidosis occurs and protrombine/INR time may be prolonged, probably due to interference with the activity of factors of the circulating coagulation. Acute kidney failure and liver damage may occur. Asthmatics can be exacerbated. Management Management must be symptomatic and supportive and must include maintaining airway pervity and monitoring heart and vital parameters until stabilization. Evaluate the administration of activated carbon if the patient occurs within 1 hour from ingestion of a potentially toxic amount. If frequent or prolonged, convulsions must be treated with diazepam or lorazepam intravenously. In case of asthma, administer bronchodilators.

Pregnancy

Inhibition of prostaglandin synthesis can have negative effects on pregnancy and/or embryo-fetal development. Epidemiological studies suggest an increased risk of abortion and heart disease and gastroschisis after the use of a prostaglandin synthesis inhibitor in the early stages of pregnancy. The absolute risk of heart failure increased from less than 1% to about 1.5%. It has been considered that the risk increases with dose and duration of therapy. In animals, the administration of prostaglandin synthesis inhibitors showed an increase in pre- and post-system loss and embryo-fetal mortality. In addition, an increase in the incidence of various malformations, including cardiovascular disease, was reported in animals to which prostaglandin synthesis inhibitors were administered during the organogenetic period. Hybuprofen should not be administered during the first and second quarter of pregnancy, if not clearly necessary. If ibuprofen is used by women who are trying to conceive, or during the first or second trimester of pregnancy, the dose must be kept as low as possible and the duration of treatment must be as short as possible. In the third trimester of pregnancy all inhibitors of the synthesis of prostaglandins can expose • the fetus to: - cardiopulmonary toxicity (with premature closure of arterial duct and pulmonary hypertension); - kidney dysfunction, which can progress to kidney failure with oligoidroamnios; • the mother and the newborn, at the end of pregnancy, to: - a possible extension of bleeding time, an anti-aggregating effect that could also occur at very low doses; - an inhibition of uterine contractions, resulting in delay or extension of labor. Consequently, ibuprofen is contraindicated during the third trimester of pregnancy (see paragraph 4.3).

Food

In limited studies, ibuprofen was found in very low-concentration breast milk and is unlikely to have adverse effects on infant breastfeeding.

Fertility

There are some evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis can compromise female fertility by affecting ovulation. This effect is reversible after the termination of treatment (see paragraph 4.4).

Source: Farmadati