ALGOFEN*12CPR RIV 200MG

ALGOFEN*12CPR RIV 200MG

Therapeutic indications

Pain of various origins and nature (headache, toothache, neuralgia, osteoarticular and muscular pain, menstrual pain).

Dosage and method of use

Dosage.Adults and children over 12 years old:1-2 coated tablets 2-3 times a day. Do not exceed the dose of 6 coated tablets per day. Do not exceed the recommended doses: elderly patients in particular should stick to the minimum dosages indicated above. Undesirable effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms (see section 4.4).Method of administration: It is advisable to take the drug on a full stomach. If the use of the medicine is necessary for more than 3 days in adolescents, or in the case of worsening of symptoms, the doctor should be consulted.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in paragraph 6.1; • Subjects with hypersensitivity to acetylsalicylic acid or other analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), particularly when hypersensitivity is associated with nasal polyposis and asthma, and presents with bronchospasm, urticaria or acute rhinitis (see also paragraph 4.4); • Do not administer to children under 12 years of age; • Severe or active peptic ulcer (see section 4.4); • History of gastrointestinal hemorrhage or perforation related to previous active treatment or history of recurrent peptic hemorrhage/ulcer (two or more distinct episodes of demonstrated ulceration or bleeding); • Hematopoietic disorders of unknown origin; • Cerebrovascular or other haemorrhage; • Disorders that lead to an increased tendency to bleeding; • Severe hepatic or renal insufficiency (see section 4.4); • Severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake); • Third trimester of pregnancy (see section 4.6); • Severe heart failure (NYHA class IV).

Side effects

The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4). Side effects are mostly dose-dependent and can vary from patient to patient. In particular, the risk of gastrointestinal bleeding is dependent on the dose and duration of treatment. After administration of ALGOFEN the following have been reported: nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4). Less frequently, gastritis has been observed. Edema, hypertension and heart failure have been reported in association with treatment with NSAIDs. Bullous reactions including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (very rarely). Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg/day), may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4). Some of the side effects listed below are less frequent when the maximum daily dose is 1200 mg compared to high-dose therapy in rheumatic patients. Adverse reactions are listed below, by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10); common (≥1/100, Infections and infestations. Very rare: worsening of inflammation associated with infection (e.g. development of necrotising fasciitis) described coinciding with the use of non-steroidal anti-inflammatory drugs¹.Pathologies of the blood and lymphatic system. Very rare: thrombocytopenia, anemia, leukopenia, pancytopenia, agranulocytosis².Immune system disorders. Uncommon: hypersensitivity reactions, including skin rash, urticaria, pruritus, purpura and asthmatic attacks (sometimes with hypotension); (see paragraph 4.4). Rare: lupus erythematosus syndrome; Very rare: anaphylactic reaction, angioedema.Psychiatric disorders. Rare: depression, confusional state, hallucinations, psychotic reactions.Nervous system disorders. Common: headache (see section 4.4), drowsiness, dizziness, fatigue, agitation, dizziness, insomnia, irritability; Uncommon: paraesthesia; Rare: aseptic meningitis³ (see section 4.4), cerebrovascular accident.Eye pathologies. Common: visual disturbances⁵; Rare: amblyopia.Ear and labyrinth disorders. Rare: tinnitus, hearing impairment.Respiratory, thoracic and mediastinal disorders. Uncommon: bronchospasm, rhinitis.Cardiac diseases. Very rare: palpitations, cardiac failure (see section 4.4), myocardial infarction, acute pulmonary edema, edema (see section 4.4).Vascular pathologies. Very rare:hypertension(see paragraph 4.4).Gastrointestinal disorders. Very common: gastrointestinal disorders, such as heartburn, dyspepsia, abdominal pain, nausea, vomiting, flatulence, diarrhoea, constipation; Common: Gastrointestinal ulcers, sometimes with bleeding and perforation (see section 4.4), occult blood loss which may lead to anemia, melena, haematemesis, ulcerative stomatitis, colitis, exacerbation of inflammatory bowel disease, complications of colonic diverticula (perforation, fistula); Uncommon:gastritis; Rare: worsening of colitis and Crohn's disease (see section 4.4); Very rare: esophagitis, pancreatitis, intestinal narrowing.Hepatobiliary disorders. Uncommon:hepatitis, jaundice, impaired liver function; Very rare: abnormal liver function tests, acute hepatitis, liver damage⁴especially in long-term use, liver failure.Pathologies of the skin and subcutaneous tissue. Common:rash; Uncommon: pruritus, purpura, photosensitivity reaction; Very rare: severe forms of skin reactions (erythema multiforme, exfoliative dermatitis, bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, alopecia, necrotizing fasciitis (see section 4.4). Severe skin infections with soft tissue complications may occur during chickenpox; Not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (PEAG).Pathologies of the musculoskeletal system and connective tissue. Not known: musculoskeletal stiffness.Renal and urinary disorders. Uncommon:development of edema, especially in patients with arterial hypertension or renal failure, nephrotic syndrome, interstitial nephritis which may be associated with renal failure⁶; Rare: renal failure, renal tissue damage (papillary necrosis⁴), increased serum uric acid concentration; Very rare: haematuria.Reproductive system and breast disorders. Very rare: menstrual disorders.Diagnostic tests. Rare: increased blood urea nitrogen, transaminases and alkaline phosphatase, decreased hemoglobin and hematocrit values, inhibition of platelet aggregation, prolonged bleeding time, decreased serum calcium, increased uric acid. ¹ This is likely related to the mechanism of action of nonsteroidal anti-inflammatory drugs. If signs of an infection appear or you notice worsening of an infection during treatment with ibuprofen, the patient is recommended to contact a doctor without delay. It will therefore be necessary to evaluate whether there is a need for anti-infective/antibiotic therapy. ² The first signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe tiredness, unexplained bruising and bleeding. These blood dyscrasias may appear particularly after long-term use of high doses. In long-term therapy, blood tests should be performed gradually (see section 4.4). ³ The first symptoms are: neck tension, headache, nausea, vomiting, fever, disorientation or clouding of consciousness. Patients with autoimmune disorders (Systemic Lupus Erythematosus, mixed connective tissue disease) appear to be predisposed (see section 4.4).⁴Particularly in long-term therapy. ⁵ Reversible eye disorders, such as toxic amblyopia, blurred vision and changes in color perception, have been observed. If such reactions occur, ibuprofen should be discontinued.⁶Varying degrees of renal function impairment may occur, particularly with long-term use of high doses. A sudden worsening of renal function may also be associated with a generalized hypersensitivity reaction.Reporting of suspected adverse reactions. Reporting suspected adverse reactions that occur after authorization of the medicinal product is important, as it allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at:https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .

Special warnings

After three days of treatment without appreciable results, consult your doctor. In asthmatic patients the product should be used with caution by consulting the doctor before taking the product. The use of ALGOFEN should be avoided concomitantly with NSAIDs including selective COX-2 inhibitors (see section 4.5). Side effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see paragraphs below on gastrointestinal and cardiovascular risks). Like other NSAIDs, ibuprofen may mask the signs and symptoms of infection due to its pharmacodynamic properties.Elderly people:Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2).Cardiovascular and cerebrovascular effects: Clinical studies suggest that the use of ibuprofen, especially at high doses (2400 mg/day) may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). In general, epidemiological studies do not suggest that low doses of ibuprofen (e.g. ≤1200 mg/day) are associated with an increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with ibuprofen only after careful consideration and high doses (2400 mg/day) should be avoided ). Careful consideration must also be exercised before starting long-term treatment in patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking habit), especially if high doses are necessary (2400 mg/ day) of ibuprofen. Before starting treatment in patients with a positive history of hypertension and/or heart failure, caution is required, since fluid retention, hypertension and edema have been reported in association with treatment with NSAIDs.Gastrointestinal effects: Gastrointestinal haemorrhage, ulceration and perforation: Gastrointestinal haemorrhage, ulceration and perforation, which may be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or previous history of serious gastrointestinal events. In the elderly and in patients with a history of ulcer, especially if complicated by haemorrhage or perforation (see section 4.3), the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5). Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal haemorrhage) particularly in the initial stages of treatment. Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or haemorrhage, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5). When gastrointestinal bleeding or ulceration occurs in patients taking ALGOFEN, treatment should be suspended. NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).Hepatic effects: When ibuprofen is prescribed to patients with impaired liver function, close medical surveillance is required, as their condition may be exacerbated. As with other NSAIDs, including ibuprofen, the values of one or more liver enzymes may increase. If ibuprofen is prescribed for a prolonged period of time, regular monitoring of liver function is indicated as a precautionary measure. If persistence or worsening of abnormal liver function values is observed, if signs or symptoms compatible with the development of liver disease develop, or if other manifestations occur (e.g. eosinophilia, rash), treatment with ibuprofen should be discontinued. Hepatitis may develop with the use of ibuprofen without prodromal symptoms. Ibuprofen is contraindicated in cases of severe hepatic insufficiency (see section 4.3). When ibuprofen is administered to patients with hepatic porphyria, caution is required as the drug may trigger an attack.Renal effects: Since fluid retention and edema have been reported in association with NSAID therapy, including ibuprofen, particular caution is required in patients with impaired cardiac and renal function, history of hypertension, elderly, patients receiving concomitant treatment with diuretics or drugs that may significantly impact renal function, and in those patients with substantial extracellular volume depletion from any cause, for example before or after major surgery. In these cases when ibuprofen is administered, monitoring of renal function is recommended as a precautionary measure. Discontinuation of treatment is usually followed by a return to the pretreatment state. Ibuprofen is contraindicated in cases of severe renal or cardiac insufficiency (see section 4.3).Severe skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported rarely in association with the use of NSAIDs including ibuprofen (see section 4.8). In the early stages of therapy, patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Acute generalized exanthematous pustulosis (PEAG) has been reported in connection with ibuprofen-containing medicinal products. ALGOFEN must be discontinued at the first appearance of signs and symptoms of severe skin reactions, such as rash, mucosal lesions or any other sign of hypersensitivity. At the first signs of hypersensitivity reactions after administration of ibuprofen, treatment should be discontinued. Medically assisted measures must be initiated by specialized medical personnel, in line with the symptoms.Pre-existing respiratory diseases:In patients with asthma, seasonal allergic rhinitis, edema of the nasal mucosa (e.g. nasal polyposis), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially if linked to symptoms similar to those of allergic rhinitis), reactions to NSAIDs such as exacerbation asthma, Quincke's edema or urticaria are more frequent than in other patients. Particular caution is recommended in these (emergency ready) patients. Ibuprofen is contraindicated in subjects with hypersensitivity to acetylsalicylic acid or other analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), in particular when hypersensitivity is associated with nasal polyposis and asthma (see section 4.3).Systemic lupus erythematosus (SLE) and mixed connective tissue disease:In patients with SLE and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see below and section 4.8).Aseptic meningitis: Aseptic meningitis has been observed very rarely in patients treated with ibuprofen. Although this is likely to occur more likely in patients with systemic lupus erythematosus and related connective tissue diseases, it has also been reported in individuals without an underlying chronic disease. The use of ALGOFEN, like any drug that inhibits the synthesis of prostaglandins and cyclo-oxygenase, is not recommended in women who intend to become pregnant. The administration of ALGOFEN should be suspended in women who have fertility problems or who are undergoing fertility investigations (see section 4.6). In dehydrated adolescents there is a risk of impaired renal function.ALGOFEN contains sucrose: Patients suffering from rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency should not take this medicine.

Pregnancy and breastfeeding

Pregnancy: Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryo/foetal development. Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk was thought to increase with the dose and duration of therapy. In animals, the administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss and embryo-foetal mortality. Furthermore, an increased incidence of various malformations, including cardiovascular malformations, has been reported in animals to which prostaglandin synthesis inhibitors were administered during the organogenetic period. During the first and second trimester of pregnancy, ALGOFEN must not be administered unless strictly necessary. If ALGOFEN is used by a woman trying to conceive, or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible. During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can expose the fetus to: • Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); • Renal dysfunction, which may progress to renal failure with oligohydramnios. The mother and the newborn, at the end of pregnancy, to: • Possible prolongation of bleeding time, and anti-aggregating effect which can occur even at very low doses; • Inhibition of uterine contractions resulting in delayed or prolonged labor. Consequently, ALGOFEN is contraindicated during the third trimester of pregnancy.Feeding time: Ibuprofen passes into breast milk in small quantities. Although no side effects in infants are known to date, caution should be used when ibuprofen is administered to a breastfeeding woman.Fertility: There is evidence to show that drugs that inhibit cyclooxygenase/prostaglandin synthesis may cause a reduction in female fertility through effect on ovulation. However, this event is reversible upon suspension of treatment.

Expiration and conservation

This medicine does not require any special storage conditions.

Interactions with other drugs

Anticoagulants:NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4). Possible interactions with coumarin-type anticoagulants must be kept in mind and therefore patients undergoing treatment with these drugs should consult their doctor before taking the product.Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs):increased risk of gastrointestinal bleeding (see section 4.4).Corticosteroids:increased risk of gastrointestinal ulceration or haemorrhage (see section 4.4).Acetylsalicylic acid:Concomitant administration of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased side effects. Experimental data suggest that ibuprofen can competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when the two drugs are administered simultaneously. Although there are uncertainties regarding the extrapolation of these data to the clinical situation, the possibility cannot be excluded that regular, long-term use of ibuprofen may reduce the cardioprotective effect of acetylsalicylic acid at low doses. No relevant clinical effects are considered likely following occasional use of ibuprofen (see section 5.1).Other NSAIDs including selective COX-2 inhibitors: avoid the concomitant use of two or more NSAIDs as this involves an increased risk of adverse effects (see section 4.4).Lithium: ibuprofen can increase plasma lithium concentrations due to reduced elimination of the latter. Therefore, monitoring of serum lithium levels is recommended.Cardiac glycosides: Ibuprofen, like other NSAIDs, can exacerbate heart failure, reduce glomerular filtration rate (GFR) and increase plasma concentrations of glycosides. Monitoring of serum glycoside levels is therefore recommended.Diuretics, ACE inhibitors, angiotensin II antagonists and beta blockers:NSAIDs can reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or an angiotensin II antagonist and agents that inhibit the cyclooxygenase system may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking ALGOFEN concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore the combination should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy. The hypotensive effect of beta-blockers may be reduced. Concomitant use of NSAIDs and beta-blockers may be associated with the risk of acute renal failure.Sulfonylureas:NSAIDs can enhance the effect of sulphonylureas. Rare cases of hypoglycemia have been reported in patients treated with sulfonylureas while taking ibuprofen.Methotrexate:NSAIDs may reduce methotrexate clearance through inhibition of tubular secretion. Administration of ibuprofen 24 hours before or after administration of methotrexate may lead to an increase in the concentration of methotrexate and an increase in its toxic effect. Therefore, the concomitant use of NSAIDs and high doses of methotrexate should be avoided. If coadministration is necessary, the patient should be carefully monitored for toxicity, especially myelosuppression and gastrointestinal toxicity. Furthermore, the potential risk of interactions must also be taken into consideration in the treatment of low doses of methotrexate (Cyclosporin and tacrolimus: the risk of a nephrotoxic effect due to cyclosporine and tacrolimus, due to the reduction of prostaglandin synthesis in the kidney, is increased by concomitant administration of some nonsteroidal anti-inflammatory drugs, including ibuprofen.Therefore, ibuprofen should be administered at lower doses than those used in patients not taking these immunosuppressive agents and renal function should be closely monitored.Fluoroquinolone antibacterials:there have been isolated cases of convulsions which may have been induced by the concomitant use of fluoroquinolone and NSAIDs.Phenytoin:When phenytoin is used concomitantly with ibuprofen, blood levels of phenytoin may increase. Monitoring of phenytoin plasma concentrations is therefore recommended.Colestipol and cholestyramine:when administered simultaneously with ibuprofen, they can delay or decrease the absorption of the latter. Therefore, it is recommended to administer ibuprofen at least 1 hour before or 4-6 hours after the administration of colestipol/cholestyramine.Potent inhibitors of CYP2C9:Coadministration of ibuprofen with CYP2C9 inhibitor agents (such as sulfinpyrazone, fluconazole and voriconazole) requires caution, as it may lead to a significant increase in peak plasma concentrations and exposure to ibuprofen, due to inhibition of ibuprofen metabolism . In a study with voriconazole and fluconazole (CYP2C9 inhibitors), an increase in S(+)-ibuprofen exposure was shown by approximately 80 to 100%. Therefore, a reduction in the dose of ibuprofen should be considered when administered concomitantly with potent CYP2C9 inhibitors, particularly when high doses of ibuprofen are administered with voriconazole or fluconazole.Zidovudine:There is an increased risk of haematological toxicity in case of concomitant administration with NSAIDs. There is evidence of an increased risk of haemarthrosis and haematomas in HIV-positive haemophilia patients treated concomitantly with zidovudine and ibuprofen.Alcohol, bisphosphonates and pentoxifylline: may potentiate gastrointestinal side effects and the risk of bleeding and ulcers.Baclofen: increased toxicity of baclofen.Plant extracts: Ginkgo Biloba may increase the risk of bleeding if taken in combination with NSAIDs.

Overdose

ToxicitySigns and symptoms of toxicity were generally not observed at doses below 100 mg/kg in children or adults. However, in some cases supportive treatment may be necessary. Children have been observed to exhibit signs and symptoms of toxicity after ingesting ibuprofen at doses of 400 mg/kg or greater.SymptomsIn cases of severe poisoning, metabolic acidosis may occur. Most patients who have ingested significant amounts of ibuprofen will experience symptoms within 4 to 6 hours. The most commonly reported overdose symptoms include: nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) effects include headache, tinnitus, dizziness, seizures (also myoclonic seizures in children), lightheadedness, and loss of consciousness. In severe poisoning, prolongation of the prothrombin time/INR may appear, probably due to interference with the actions of circulating coagulation factors. Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnea, cyanosis, diarrhea, and CNS and respiratory depression have also been reported rarely. Disorientation, arousal, fainting and cardiovascular toxicity including hypotension, bradycardia, tachycardia have been reported. In asthmatic patients, an exacerbation of the condition is possible. In cases of significant overdose, renal failure and liver damage are possible.TreatmentThere is no specific antidote for ibuprofen overdose. In case of overdose, symptomatic and supportive treatment is therefore indicated. Particular attention is due to the control of blood pressure, acid-base balance and any gastrointestinal bleeding. Administration of activated charcoal should be considered within one hour of ingesting a potentially toxic amount. Alternatively, in adults, gastric lavage should be considered within one hour of ingesting a potentially life-threatening overdose. Adequate diuresis must be ensured and renal and hepatic functions must be closely monitored. The patient must remain under observation for at least four hours following ingestion of a potentially toxic amount of drug. Any occurrence of frequent or prolonged convulsions should be treated with intravenous diazepam. Depending on the patient's clinical condition, other support measures may be necessary. For more information, contact your local poison control center.

Active principles

One coated tablet contains:Active principle:ibuprofen 200 mg. Excipient with known effects: sucrose. For the full list of excipients, see section 6.1.

Excipients

Corn starch, stearic acid, croscarmellose sodium, colloidal anhydrous silica, povidone, carmellose sodium, shellac, gum arabic, titanium dioxide, calcium sulphate, sucrose, carnauba wax.