ALGIDRIN OS 120ML 20MG/ML+SIR

ALGIDRIN 20 MG/ML ORAL SOSPENSION, CHILDREN

active ingredients

Each ml of oral suspension contains: 20 mg of ibuprofen (supplied by 34.17 mg of lysine ibuprofen). Excipients with known effects: Sorbitol (E-420) 25 mg, maltitol (E- 965) 100 mg, Allura AC red colorant (E129) 0.0786 mg, methyl para-hydroxybenzoate (E-218) 1.45 mg, etyle para-hydroxybenzoate (E-214) 0.32 mg, propile para-hydroxybenzoate (E-216) 0.22 mg. For the full list of excipients, see the section 6.1.

Excellent

Purified water, Microcrystalline cellulose, Carboxyethylcellulose sodium, Sorbitol (E-420), Maltitol (E-965), Beta-cyclodextrin, Sodium saccharin, Sucralose (E-955), Aroma wood fruits, Allura-AC red colorant (E-129), Para-hydroxybenzoate of methyl (E-218), Para-iron.

Therapeutic indications

ALGIDRIN is indicated for children over 3 months and adolescents: • for symptomatic treatment of fever • for symptomatic treatment of mild to moderate pain

Contraindications

- Hypersensitivity to ibuprofen, any other NSAID or any of the excipients listed in the paragraph 6.1. - Patients who have developed allergic reactions, asthma attacks, acute rhinitis, urticaria or angioneurotic edema after being taken substances with similar actions (e.g. acetylsalicylic acid or other anti-inflammatory drugs). - A history of gastrointestinal hemorrhage or perforation related to previous treatments with non-steroidal anti-inflammatory drugs (NSAID). - Peptic ulcer, active or recurrent gastrointestinal hemorrhage (two or more separate episodes verified by ulceration or hemorrhage). - Patients with diseases that tend to increase bleeding. - Severe heart failure (NYHA: class IV). - Severe kidney failure (glomerular filtration speed below 30 ml/min). - Severe liver failure. - Patients with severe dehydration (caused by vomiting, diarrhea or insufficient intake of liquids). - During the third trimester of pregnancy (see paragraph 4.6).

Population

Population: It must be taken the lowest effective dose, as soon as possible, necessary to control symptoms (see section 4.4) Pediatric population: The dose of ibuprofen to be administered depends on the age and weight of the child. For children aged between 3 months and 12 years, the recommended daily dose of ibuprofen ranges from 20 to 30 mg/kg body weight, divided into three or four individual doses (see table below). The use of this medicine is not recommended in children under 3 months of age or under 5 kg of body weight. The interval between doses depends on the course of symptoms, but should never be less than 4 hours. The following posological scheme is recommended as a guideline. The doses can be repeated every 6-8 hours, without exceeding the daily amounts indicated in the last column:

POSOLOGY FOR CHILDREN
Age/weight	Frequency	Dose	Maximum daily dose
From 3 to 6 months From 5 to 7,6 kg approximately	3 times a day	50 mg (2.5 ml) / dose	150 mg (7,5 ml)
From 6 to 12 months From 7,7 to 9 kg approximately	3 to 4 times a day	50 mg (2.5 ml) / dose	150-200 mg (7,5-10 ml)
From 1 to 3 years From 10 to 15 kg approximately	3 to 4 times a day	100 mg (5 ml) / dose	300-400 mg (15-20 ml)
From 4 to 6 years From 16 to 20 kg approximately	3 to 4 times a day	150 mg (7,5 ml) / dose	450-600 mg (22.5-30 ml)
From 7 to 9 years From 21 to 29 kg approximately	3 to 4 times a day	200 mg (10 ml) / dose	600-800 mg (30-40 ml)
From 10 to 12 years From 30 to 40 kg approximately	3 to 4 times a day	300 mg (15 ml) / dose	900-1200 mg (45-60 ml)

Teenagers (over 12 years of age): The recommended dose is 10-20 ml (equivalent to 200-400 mg of ibuprofen) every 4-6 hours, if necessary, without exceeding the daily dose of 1200 mg of ibuprofen in 24 h. Given the quantity of ibuprofen in this medicinal product, the use of other packages with more suitable doses is recommended for the treatment of adults and adolescents over 12 years of age. Renal insufficiency: Some precautions should be taken when using non-steroidal anti-inflammatory drugs (NSAID) in patients with kidney failure, since ibuprofen is generally eliminated renally. Lower doses are used for patients with mild to moderate kidney dysfunction. Hybuprofen should not be used in patients with severe kidney failure (see paragraph 4.3). Hepatic insufficiency: Although differences in the pharmacokinetic profile of ibuprofen have not been observed in patients with liver failure, it is advisable to take precautions in the use of NSAIDs in this type of patients. Patients with mild to moderate liver failure should start treatment at lower doses and be carefully monitored. Hybuprofen should not be used in patients with severe liver failure (see paragraph 4.3). Method of administration: This medicine is administered by mouth. It can be administered directly or diluted with water. Shake the bottle before use. The packs contain a 5 ml graduated syringe for oral use, for an accurate dosage. The syringe should be released from the bottle, dismantled, washed and dried well after each use. Patients with gastric problems should take the medicine during meals.

Conservation

Do not store at a temperature greater than 30°C.

Warnings

Masking symptoms of underlying infections: ALGIDRIN can mask the symptoms of infection, which can lead to a delay in the beginning of the appropriate treatment and therefore worsen the outcome of the infection. This was observed in bacterial pneumonia acquired in communities and in bacterial complications of chickenpox. When ALGIDRIN is administered to relieve fever or pain in relation to the infection, it is recommended to monitor the infection. In non-hospital environments, the patient should consult a doctor if symptoms persist or worsen. The adverse reactions caused by the combination of the active ingredient and the concomitant consumption of alcohol, in particular reactions related to the gastrointestinal tract or the central nervous system, can be increased by the use of NSAIDs. Gastrointestinal hazards: Gastrointestinal hemorrhages, ulcers and perforations: during treatment with NSAIDs, including ibuprofen, reports of gastrointestinal hemorrhages, ulcers and perforations (which may be fatal) at any time, with or without prior warning symptoms and with or without a previous history of serious gastrointestinal events. The risk of gastrointestinal hemorrhage, ulcer or perforation is greater with increasing doses of NSAID, in patients with a history of ulcer, especially if ulcers are complicated by hemorrhage or perforation (see paragraph 4.3) and in elderly patients. These patients must begin treatment with the lowest possible dose and should be prescribed to them concomitant treatment with protective agents (e.g. misoprostol or protonic pump inhibitors); combined treatment should also be considered for patients requiring low doses of acetylsalicylic acid or other medicines that may increase gastrointestinal risk factors (see paragraph 4.5). Patients with a history of gastrointestinal toxicity, and especially elderly patients, should be advised to immediately consult a doctor in case of non-frequent abdominal symptoms (especially gastrointestinal bleeding) during treatment and especially during early stages. Special caution is recommended for patients who receive concomitant treatments that may increase the risk of gastrointestinal ulcer or bleeding such as dicumarin-based oral anticoagulants or antipystronic agents such as acetylsalicylic acid (see paragraph 4.5). In addition, some precautions should be taken in case of concomitant administration of oral corticosteroids and antidepressants selective serotonin reuptake inhibitors (SSRIs). Treatment should be stopped immediately in case of gastrointestinal hemorrhage or ulcer in patients under treatment with this medicine (see paragraph 4.3). NSAIDs should be given with caution in patients with a history of ulcerative colitis or Crohn's disease, as they may aggravate these conditions (see paragraph 4.8). Cardiovascular and cerebrovascular risk: Particular attention should be paid to patients with history of hypertension and/or heart failure since fluid retention and edema were associated with treatments with NSAIDs. Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg per day), may be associated with a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). In general, epidemiological studies do not suggest that ibuprofen at low doses (e.g. 1,200 mg/die) is associated with an increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), proven ischemic cardiopathy, peripheral artery disease and/or cerebrovascular disease, should be treated with ibuprofen only after careful evaluation and avoiding high doses (2400 mg/die). A careful assessment must also be made before starting long-term treatment in patients with risk factors of cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if they require high doses of ibuprofen (2400 mg/die). Risk of severe skin reactions: Very rare reports of severe skin reactions were received, some fatal, including exfoliative dermatitis, Stevens-Johnson's syndrome and toxic epidermal necrolysis in association with FANS use (see paragraph 4.8). Patients seem to be more at risk of these reactions at the beginning of treatment: in most cases these side effects appear during the first month of treatment. Generalized acute exantematic pustolosis (Acute Generalized Exanthematous Pustulosis - AGEP) in relation to products containing ibuprofen. The administration of the medicinal product must be immediately interrupted to the first symptoms of skin erythema, mucosa lesions or other signs of hypersensitivity. On exceptional occasions, chickenpox can cause infectious complications of skin and soft tissue. To date, it is not possible to exclude the role of NSAIDs in exacerbating these infections. Therefore the ibuprofen should be avoided in case of chickenpox. Allergic reactions: On very rare occasions severe acute hypersensitivity reactions were observed (e.g. anaphylactic shock). Treatment should be interrupted when the first signs of a hypersensitivity reaction appear after taking / administering ibuprofene. According to the symptoms, the necessary medical measures must be initiated by the specialized staff. Caution is required in patients who have suffered from hypersensitivity or allergic reactions to other substances, since this may increase the risk of hypersensitivity reactions to ibuprofen. Caution is required in patients suffering from seasonal allergies, nasal polyps or chronic obstructive respiratory disorders, since there is a high risk of allergic reactions. These reactions may occur as asthma, edema of Quincke or hives. Kidney and/or hepatic insufficiency: Hybuprofen should be used with caution in patients with liver or kidney disease, especially during simultaneous treatment with diuretics, as inhibition of prostaglandins can produce fluid retention and compromise kidney function. If given to these patients, the dose of ibuprofen should be as low as possible and the kidney function should be monitored regularly. There is a risk of renal impairment in children, adolescents and dehydrated elderly patients. In case of dehydration, ensure adequate intake of liquids. Special precautions must be taken in children with severe dehydration, for example due to diarrhea, since dehydration could act as a triggering factor in the development of kidney failure. In general, the usual use of analgesics, in particular the combination of different analgesic substances, can cause lasting kidney injury, with a risk of kidney failure (analgesic nephropathy). Like other NSAIDs, long-term treatments with ibuprofen can cause kidney papillar necrosis and other kidney disease. Renal toxicity has also been observed in patients whose kidney prostaglandins play a compensatory role in renal perfusion. Senior patients, patients with kidney failure, heart failure, liver dysfunction and those treated with diuretics or antihypertensives (ACE inhibitors) have a high risk of manifesting this reaction. Breaking NSAID therapy normally restores the state before treatment. Like other NSAIDs, ibuprofen can produce slight transient increases in certain hepatic parameters and significant increases in AST and ALT levels. The treatment must be suspended in the event of a significant increase in these parameters (see paragraphs 4.2 and 4.3). Use in the elderly population: Older patients suffer from increased adverse reactions to NSAIDs, particularly hemorrhages and gastrointestinal perforations, which may be fatal (see paragraph 4.2). Other: As with other NSAIDs, anaphylactic/anaphylactic reactions can occur without a previous exposure to the drug. It must be used with precaution even in patients with a history of bronchial asthma, chronic rhinitis and allergic diseases, since in these types of patients cases of bronchospasm, hives and angioedema have been reported (see paragraph 4.3). On rare occasions, cases of aseptic meningitis were reported with the use of ibuprofen. In most cases, patients suffered from some form of autoimmune disease (such as systemic lupus erythematosus or other connective tissue diseases), which represented a risk factor, although cases were reported in patients without chronic disease (see paragraph 4.8). The observed symptoms of asyptic meningitis were torcicollo, headache, nausea, vomiting, fever and disorientation. Special medical control is required during administration to patients immediately after major surgery. Like other NSAIDs, it should only be used after a rigorous assessment of the risk/benefit profile in patients with acute intermittent porphyria. Renal and hepatic function, hematological function and erythrocyte count should be controlled as a precautionary measure in long-term treatment patients, since ibuprofen, like other NSAIDs, may inhibit pyasternic aggregation and prolong bleeding time. Undesirable effects can be minimized by using the minimum effective dose for a short period as possible. Warnings on excipients: This medicine can produce allergic reactions because it contains Allura AC red colorant (E-129). It can cause asthma, especially in patients allergic to acetylsalicylic acid. This medicine contains maltitol (E-965) and every ml of suspension contains 25 mg of sorbitol (E-420). Patients with hereditary intolerance to fructose should not take this medicine. This medicine contains methyl para-hydroxybenzoate (E-218), etyle para-hydroxybenzoate (E-214) and propyle para-hydroxybenzoate (E-216) and can produce allergic reactions (possibly delayed). Interference with analytical tests: Time of bleeding (can be prolonged for 1 day after suspension of treatment). Blood sugar levels (can be reduced). Creatine clearance (can be reduced). Ematocrite or hemoglobin levels (can be reduced). Concentrations of urethic nitrogen in the blood and serum concentrations of creatinine and potassium (can be increased). Tests of liver function: increased transaminase values.

Interactions

In general, NSAIDs must be taken with precaution if used along with other drugs that can increase the risk of gastrointestinal ulcer, gastrointestinal hemorrhage and kidney dysfunction. Interactions with the following medicines have been reported: - Diuretics : they can increase the nephrotoxicity of NSAIDs, as a result of the reduction of kidney blood flow. As with other NSAIDs, concurrent treatment with potassium-saving diuretics can be associated with an increase in potassium levels, making it necessary to monitor the plasma levels of this ion. - Anticoagulants: nSAIDs may increase the effects of dicoumarin anticoagulants such as warfarin (see section 4.4.).- Antiplatelet agents : increase the risk of gastrointestinal bleeding (see section 4.4).NSAIDs should not be combined with ticlopidine, due to the risk of an additive effect in inhibiting platelet function Courtesy: may also increase the risk of gastrointestinal ulcer or bleeding (see paragraph 4.4). - Selective serotonin reuptake inhibitors (SSRIs) : may also increase the risk of gastrointestinal bleeding (see paragraph 4.4). - Antihypertensive agents (including ACE inhibitors, beta-blockers and angiotensin II receptor antagonists) : NSAIDs may reduce the efficacy of antihypertensive agents, including ACE inhibitors or beta-blocking agents and angiotensin II antagonists.Concomitant treatment with NSAIDs, ACE inhibitors, beta-blockers or angiotensin receptor blockers may be associated with the risk of acute renal disease, including acute renal failure, which is usually reversible.Therefore, the combination should be administered with caution, especially in elderly patients.Patients should be well hydrated and regular monitoring of renal function should be considered after initiation of concomitant treatment.- Acetylsalicylic acid and other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors): simultaneous use should be avoided, since the administration of several NSAIDs may increase the risk of gastrointestinal ulceration and bleeding.- Acetylsalicylic acid : In general, concomitant administration of ibuprofen and acetylsalicylic acid is not recommended due to the potential for increased adverse effects.Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered concomitantly.Although there are uncertainties regarding the extrapolation of these data to clinical situations, the possibility that long-term regular use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded.There is likely to be no clinically relevant effect with occasional use of ibuprofen (see section 4.4) 5.1.).- Lithium : NSAIDs can increase plasma levels of lithium, probably due to a decrease in its kidney clearance. Joint administration should be avoided unless lithium levels are monitored. It must be considered a reduction in the lithium dose. - Methotrexate given at doses of 15 mg/week or greater : If NSAIDs and methotrexate are administered within 24 hours, an increase in plasma levels of methotrexate may occur (NSAIDs appear to reduce the tubular secretion and renal clearance of methotrexate), with an increased risk of methotrexate toxicity.Therefore, the use of ibuprofen in patients receiving high-dose methotrexate treatment should be avoided.- Metotrexate administered at low doses, below 15 mg/week : ibuprofen increases metotrexate levels. If used in association with metotrexate at low doses, the patient's blood chemistry should be closely monitored, especially during the first weeks of simultaneous administration. Supervision should also be increased in case of compromised kidney function, even minimal, and in elderly patients. The renal function should be monitored to prevent any possible decrease in metotrexate clearance. - Sulfaniluree: the NSAIDs can strengthen the effect of sulfaniluree. Rare cases of hypoglycemia have been reported in patients treated with sulfaniluree and ibuprofene. - Mifepristone: theoretically, the effectiveness of this drug can be reduced due to the antiprostaglandiniche properties of the NSAIDs. Limited evidence suggests that the concomitant administration of an NSAID on the same day of prostaglandin has no negative impact on the effects of mifepristone or prostaglandin in cervical maturation or in uterine contractility and does not reduce clinical effectiveness in abortion induction. - Heart glycosides (digoxin): nSAIDs can exacerbate heart failure, reduce glomerular filtration speed and increase heart glycoside levels, thus increasing the risk of digoxin toxicity. - Pentoxins: the risk of hemorrhage can increase in patients receiving ibuprofen in combination with pentoxyphylline. Therefore, the monitoring of bleeding time is recommended. - Probenecid and Finpirazoni : can cause an increase in plasma concentrations of ibuprofen; this interaction can be due to an inhibitory mechanism at the level of the secretion of the renal tubule and glucuronidation, and it may be necessary to adjust the dose of ibuprofen. - Chinolonic Antibiotics: data from animal studies indicate that NSAIDs can increase the risk of seizures associated with the use of kinolonic antibiotics. Patients who have taken NSAIDs and chinoloni may have a higher risk of manifesting seizures. - Idantoine (fenitoin) and sulfamidic: toxic effects of these substances can be increased. During simultaneous treatment with ibuprofen, plasma levels of phenytoin can increase. - Colestiramine: concurrent administration of ibuprofen and choleramine can reduce the absorption of ibuprofen in the gastrointestinal tract, although clinical relevance is not known. - Tacrine: the administration of ibuprofen along with tacrine increases the toxicity of tacrine, with episodes of delirium, due to the possible inhibition of its bond with plasma proteins. - Ciclosporine, tacrolimus: simultaneous administration of NSAIDs can increase the risk of nephrotoxicity due to a reduction in renal synthesis of prostaglandins. If administered in conjunction, the kidney function should be closely monitored. - Trombolites: the risk of hemorrhage can increase. - Zidovudina: the risk of hematological toxicity can increase when NSAIDs are administered along with zidovudine. There is a greater risk of joint bleeding and hematomas in HIV patients (+) with hemophilia that receive concomitant treatment with zidovudine and ibuprofen. - Aminoglycosides: nSAIDs can reduce the excretion of aminoglycosides. - Herbal Extracts: Ginkgo biloba can increase the risk of hemorrhage with FANS - Other: concurrent use of alcohol can increase adverse effects related to the use of NSAIDs, especially those involving the gastrointestinal tract and the central nervous system (see paragraphs 4.4 and 4.8). - Food: the administration of ibuprofen with food reduces the absorption rate, although this has no effect on the extent of absorption (see paragraph 5.2). - CYP2C9 inhibitors: administration of ibuprofen with CYP2C9 inhibitors can increase exposure to ibuprofen (substrate of CYP2C9). A study with voriconazole and fluconazole (CYP2C9) inhibitors showed an increase from 80% to 100% of exposure to ibuprofene S (+). A lower dose of ibuprofen should be taken into account when administered in conjunction with a powerful CYP2C9 inhibitor, especially when ibuprofen is given at high doses with voriconazole or fluconazole.

Effects

The most frequently observed side effects are gastrointestinal. Peptide ulcers, drilling or gastrointestinal hemorrhage, in some fatal cases, may occur, especially in the elderly (see paragraph 4.4). There were also reported cases of nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, ematemesis, ulcerative stomatitis and exacerbation of colitis and Crohn's disease (see paragraph 4.4). The appearance of gastritis was observed less frequently. The side effects are reported by organ or system and depending on the frequency according to the following classification: very common (≥ 1/10); common (≥1/100, gastrointestinal pathologies. Common: dyspepsia, diarrhea, nausea, vomiting, abdominal pain, flatulence, constipation, melena, ematemesis, gastrointestinal hemorrhage; Not common: gastritis, duodenal ulcer, gastric ulcer, mouth ulcer, gastrointestinal perforation; Very rare: pancreatititis; Frequency not known: exacerbation of colitis, Crohn's disease. Skin disorders and hypersensitivity reactions. Not common: rash, hives, itching, purple (including allergic purple), photosensitivity reaction; Very rare: Bollose reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, multiform erythema. Severe infections of the skin and complications of soft tissues may occur exceptionally during the chickenpox (see also “Infections and infestations” and paragraph 4.4). Frequency not known: reaction to the drug with heosinophilic and systemic symptoms ( Dress syndrome). Generalized acute acute exantelosis (AGEP). Infections and infestations1. Not common: rhinitis; Rare: aseptic meningitis (see paragraph 4.4). Immune disorders. Not common: hypersensitivity2; Rare: anaphylactic reaction: symptoms may include swelling of the face, tongue and larynx, dispnea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock). central nervous system pathologies. Municipalities: headaches, dizziness; Not common: paresthesia, drowsiness; Rare: optic neuritis. Psychiatric disorders. Not frequent: insomnia, anxiety; Rare: depression, confusion, disorientation. Ear and labyrinth pathologies. Not common: hearing disorders; Rares: vertigo, tinnitus. Pathologies of the eye. Not common: visual alterations; Rare: reversible toxic ambliopia. Respiratory, thoracic and mediastinic pathologies. Not common: asthma, bronchospasmo, dispnea. Diseases of the emolinfopoietic system. Rares: thrombocytopenia, leucopenia, neutropenia, agranulocytosis, aplastic anemia and hemolytic anemia. The initial symptoms are: fever, sore throat, superficial ulcers of the mouth, flu-like symptoms, excessive fatigue and bleeding of the nose and skin for unknown causes. Heart disease. Very rare: myocardial infarction heart failure (see paragraph 4.4). Vascular diseases⁴. Very rare: hypertension. Hepatobile pathologies. Not common: hepatitis, jaundice, hepatic dysfunction; Rare: liver failure; Very rare: liver failure. Kidney and urinary pathologies. Not common: interstitial nephritis, nephrosic syndrome, kidney failure, acute kidney failure, papillar necrosis (especially after prolonged use), associated with increased uretha. Systems pathologies. Common: fatigue; Rare: edema. 1Infections and infestations: in conjunction with the use of NSAIDs, an exacerbation of inflammations related to infections (e.g. necrotizing fascites) was reported. You should consult a doctor as soon as possible if there are signs or worsening of the infection during the use of ibuprofen. 2 Hypersensitivity: hypersensitivity reactions were observed after treatment with NSAIDs. These may consist of: (a) non-specific allergy of the respiratory tract and anaphylaxis; (b) reactivity of the respiratory tract asthma, aggravated asthma, bronchospasm or dispnea; o (c) various skin alterations, including rash of various types, itching, purple, angioedema and, in very rare cases, multiform erythema and dermatosis (including Stevens-Johnson syndrome, epidermal toxic necrosis). ^3,4 Heart and vascular disease: clinical studies suggest that the use of ibuprofen, especially at high doses (2,400 mg per day) may be associated with a small increase in the risk of arterial thrombotic events (such as myocardial infarction or stroke, see paragraph 4.4). 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: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .

Overdosing

Most cases of overdose are asymptomatic. Generally no signs of toxicity were observed at doses of less than 100 mg/kg in children and adults. However, additional assistance may be required in some cases. It has been observed that children show signs and symptoms of toxicity after ingesting quantities equal to or greater than 400 mg/kg. Synonyms Most patients who have taken significant amounts of ibuprofen have shown symptoms within the next 4-6 hours. The most frequently reported symptoms in case of overdose include abdominal pain, nausea, vomiting, lethargy, drowsiness. The effects on the central nervous system (SNC) include headaches, tinnitus, dizziness, seizures, loss of consciousness and ataxia. In addition, rare cases of nistagm, metabolic acidosis, hypothermia, alterations of the kidney function, gastrointestinal hemorrhage, coma, apnea and depression of the central nervous and respiratory system were reported. Cases of cardiovascular disease have been reported, including hypotension, bradycardia and tachycardia. In case of severe poisoning, metabolic acidosis may occur. In case of severe overdose, kidney and liver damage may occur. Therapeutic measures for overdose: Treatment is symptomatic and no specific antidote is available. For quantity in which it is unlikely that the symptoms manifest (less than 50 mg/kg of ibuprofen) can be administered water to reduce as much gastrointestinal discomfort as possible. If large quantities have been ingested, active carbon must be administered. Emptying the stomach with vomiting should only be taken into account within 60 minutes of ingestion. Therefore, the gastric lavender should not be taken into account unless the patient has ingested a dangerous amount for the life of the drug and have spent less than 60 minutes from ingestion. The benefit of measures such as forced diuresis, hemodialysis or hemoperfusion is questionable, since ibuprofen strongly binds to plasma proteins.

Pregnancy

. 1) First and second quarter of pregnancy: The inhibition of the synthesis of prostaglandins adversely affects pregnancy and/or the development of embryo/fetus. Data from epidemiological studies suggest an increase in the risk of miscarriage and heart and gastroschisis malformations, after the use of an inhibitor of the synthesis of prostaglandins in the early stages of pregnancy. The absolute risk of heart failure has increased from less than 1% to about 1.5%. The risk seems to increase with dose and duration of treatment. In animals, the administration of a prostaglandin synthesis inhibitor has shown to produce an increase in pre- and post-system losses and embryo/ fetal mortality. In addition, cases of increase in the incidence of different malformations, including cardiovascular malformations, in animals to which an inhibitor of the synthesis of prostaglandins was given during the organogenic period. Hybuprofen should not be administered during the first and second quarter of pregnancy unless it is considered strictly necessary. If ibuprofen should be used in a woman who is trying to get pregnant, or during the first and second trimester of pregnancy, the dose and duration of treatment should be reduced as much as possible. 2) Third quarter of pregnancy: During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can exhibit: - Fetus a: - cardiopulmonary toxicity (with premature closure of arterial duct and pulmonary hypertension); - kidney dysfunction, which can evolve in kidney failure with oligoidramnios. - The mother, at the end of pregnancy, to: - possible extension of bleeding time and antiplatelet effect, which can also occur at very low doses; - inhibition of uterine contractions resulting in delayed or prolonged birth (with a tendency towards greater bleeding in the mother and child). Therefore, this medicine is contraindicated during the third trimester of pregnancy (see paragraph 4.3).

Breastfeeding

: Hybuprofen and its metabolites enter breast milk at low concentrations. To date, no harmful effects were found for infants, so in general breastfeeding should not be interrupted during short-term treatment at the recommended dose for pain and fever.

Fertility

: The use of ibuprofen can alter female fertility and is not recommended in women seeking to remain pregnant. Women with difficulty in conception or subject to fertility tests should consider the suspension of this medicine.

Source: Farmadati