Spididol 400mg 12 coated tablets

In compliance with article 118 "authorization of advertising to the public" of the legislative decree of 24 April 2006, number 219

INDICATIONS

Pain of various origins and nature: headache, toothache, neuralgia, osteo-articular and muscular pain, menstrual pain. Adjuvant in the symptomatic treatment of feverish and flu states.

CONTRAINDICATIONS

• Hypersensitivity to the active ingredient or to other substances closely related from a chemical point of view and/or to any of the excipients listed in paragraph 6.1. • History of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). • History of recurrent peptic hemorrhage/ulcer (two or more distinct episodes of demonstrated ulceration or bleeding). • Active and recurrent peptic ulcer. • Gastrointestinal bleeding • Other ongoing bleeding such as cerebrovascular bleeding • Ulcerative colitis and Crohn's disease. • Severe hepatic and/or renal failure • Hemorrhagic diathesis • Severe heart failure (NYHA class IV). • Due to the possibility of cross-allergic reactions with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, the product is contraindicated in patients in whom said drugs induce allergic reactions such as bronchospasm, asthma, urticaria, rhinitis, nasal polyposis, angioedema. • In case of systemic lupus erythematosus and collagen diseases, the doctor should be consulted before using SPIDIDOL. • The granules, as they contain aspartame, are contraindicated in patients suffering from phenylketonuria. • Third trimester of pregnancy (see par. 4.6). • Before or after cardiac surgery.

WARNINGS AND PRECAUTIONS FOR USE

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below Gastrointestinal and cardiovascular risks). Adequate monitoring and appropriate instructions are necessary in patients with a history of hypertension and/or mild to moderate congestive heart failure since fluid retention and edema have been found in association with treatment with NSAIDs. 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 patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking habit) on long-term treatment, especially if high doses (2400 mg/day) of ibuprofen are necessary. The use of SPIDIDOL should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors. In dehydrated adolescents there is a risk of impaired renal function. Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2). Gastrointestinal haemorrhage, ulceration and perforation: Gastrointestinal haemorrhage, ulceration and perforation, which may be fatal, have been reported at any time during treatment with all NSAIDs, 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. The concomitant use of protective agents (misoprostol or proton pump inhibitors) must 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 par. 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. At daily doses above 1000 mg ibuprofen can prolong bleeding time. Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, 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 SPIDIDOL, treatment should be suspended. NSAIDs should be administered with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8). Severe skin reactions Severe skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic necrolysis epidermal, have been reported very rarely in association with the use of NSAIDs (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. SPIDIDOL should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Hepatotoxic reactions may occur in the setting of generalized hypersensitivity reactions. Caution must be taken in the treatment of patients with a history of bronchospasm, especially following the use of other drugs, and in those with coagulation disorders and with reduced renal and/or hepatic or cardiac function. In such patients it is advisable to resort to periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment (see section 4.2). In patients suffering from or with a history of bronchial asthma or allergic disease, bronchospasm may worsen. Systemic lupus erythematosus or other collagen diseases constitute risk factors for serious manifestations of generalized hypersensitivity, therefore caution is required in patients with these pathologies. Since ocular alterations have been detected, although very rarely, during treatment with ibuprofen, it is recommended that in the event of the onset of visual disturbances, treatment should be interrupted and an ophthalmological examination be carried out. The use of SPIDIDOL, as with any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women intending to become pregnant, as it may cause impairment of female fertility through an effect on ovulation. The administration of SPIDIDOL must be suspended in women who have fertility problems or who are undergoing fertility investigations (see section 4.6). Caution should be used when initiating treatment with ibuprofen in patients with severe dehydration. Masking the symptoms of underlying infections SPIDIDOL may mask the symptoms of infection, which may delay the initiation of appropriate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. In isolated cases, an exacerbation of infectious inflammations (e.g. development of necrotizing fasciitis) in temporal correlation with NSAIDs has been described. Therefore, ibuprofen therapy should be used with caution in patients suffering from infection. When SPIDIDOL is administered for the relief of fever or pain related to infection, monitoring of the infection is recommended. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen. NSAIDs may cause an increase in liver function test results. Alcohol consumption should be avoided as it can intensify the side effects of NSAIDs, especially those affecting the gastrointestinal tract or central nervous system. Medically assisted measures must be initiated by specialized medical personnel, in line with the symptoms. Acid ibuprofen can cause a prolongation of the bleeding time by reversibly inhibiting the aggregation of platelets. SPIDIDOL contains sucrose. Patients suffering from rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. SPIDIDOL contains 56.98 mg and 82.98 mg of sodium respectively for the granules and tablet packs, and equivalent respectively to 2.85% and 4.15% of the maximum daily intake recommended by WHO which corresponds to 2 g of sodium per adult. This information must be taken into consideration in the case of patients who are following a low-sodium diet. SPIDIDOL contains 60 mg of aspartame per sachet for the packs of cola-lemon flavor and apricot flavor granules. Aspartame ingested orally is hydrolyzed in the gastrointestinal tract. Phenylalanine is the main product of its hydrolysis.

INTERACTIONS

Diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may 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) co-administration of an ACE inhibitor or an angiotensin II antagonist and agents that inhibit the cyclo-oxygenase 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 SPIDIDOL 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. Corticosteroids: increased risk of gastrointestinal ulceration or haemorrhage (see section 4.4). Anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4). The prothrombin time must be carefully monitored during the first weeks of combined treatment and the dosage of anticoagulants may require adjustment. Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4). Furosemide and thiazide diuretics: A reduction in the efficacy of furosemide and thiazide diuretics may occur, probably due to sodium retention associated with inhibition of renal prostaglandin synthetase.Beta blockers: 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. Other non-steroidal anti-inflammatory drugs (NSAIDs) including selective COX-2 inhibitors: Ibuprofen should be used with caution in combination with other NSAIDs because it may increase the risk of adverse reactions in the gastrointestinal tract. 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 effect is considered probable following occasional use of ibuprofen (see section 5.1). Digoxin, phenytoin and lithium: Isolated cases of elevated plasma levels of digoxin, phenytoin and lithium as a result of combined therapy with ibuprofen are reported in the literature. Methotrexate: Ibuprofen may cause an increase in plasma levels of methotrexate. Zidovudine: Concomitant therapy with Zidovudine and ibuprofen may increase the risk of hemarthrosis and hematoma in HIV(+) hemophiliac patients. Tacrolimus: the concomitant use of ibuprofen and tacrolimus may increase the risk of nephrotoxicity due to the reduction in renal synthesis of prostaglandins. Hypoglycemic drugs: ibuprofen increases the hypoglycemic effect of oral hypoglycemic drugs and insulin. The dosage may need to be adjusted. Cyclosporine: Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to an increased risk of ciclosporin nephrotoxicity. Voriconazole or fluconazole: Concomitant use of ibuprofen may result in an increase in ibuprofen exposure and plasma concentration. Mifepristone: Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to increased exposure to NSAIDs. A decrease in the efficacy of mifepristone may theoretically occur due to the antiprostaglandin properties of NSAIDs. Some studies on the effect of single or repeated administration of ibuprofen starting from the day of prostaglandin administration (or when necessary) have found no evidence of a negative influence on the action of mifepristone, and on the overall clinical efficacy of the pregnancy termination protocol. Quinolone antibiotics: Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to an increased risk of seizures. Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding with NSAID medications. Alcohol, bisphosphonates and pentoxifylline: may potentiate gastrointestinal side effects and the risk of bleeding and ulcers. Baclofen: high toxicity of baclofen. Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides. Interactions with diagnostic test results: - Bleeding time (may prolong bleeding time up to 1 day after discontinuation of therapy), - Serum glucose concentrations (may decrease), - Creatinine clearance (may decrease), - Hematocrit or hemoglobin (may decrease), - BUN, serum creatinine and potassium concentrations (may increase), - Liver function tests (an increase in transaminases may occur).

SIDE EFFECTS

Side effects are mainly related to the pharmacological effect of ibuprofen on the synthesis of prostaglandins. Gastrointestinal disorders: 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). After administration of SPIDIDOL the following have been reported: nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, heartburn, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4). Less frequently, gastritis has been observed. Skin and subcutaneous tissue disorders: Bullous reactions including Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis (very rarely) and drug reactions with eosinophilia and systemic symptoms (DRESS syndrome). Cardiac and vascular pathologies: Edema, hypertension and heart failure have been reported in association with treatment with NSAIDs. 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). Below is a table relating to the frequency of adverse events: Frequency: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000,<1/1000); very rare (<1/10000); not known (cannot be estimated from the available data)

Classification by organs and systems | Frequency

Gastrointestinal disorders

Dyspepsia, diarrhea | Frequency: Very common

Abdominal pain, heartburn, nausea, flatulence, abdominal discomfort | Frequency: Municipality

Peptic ulcers, gastrointestinal haemorrhage, vomiting, melena, gastritis, stomatitis | Frequency: Uncommon

Gastrointestinal perforation, constipation, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease | Frequency: Rare

Anorexia | Frequency: Not known

Systemic pathologies and conditions relating to the administration site

Edema, fever | Frequency: Not known

Cardiac diseases

Heart failure | Frequency: Not known

Vascular pathologies

Hypertension, arterial thrombosis, hypotension | Frequency: Not known

Nervous system disorders

Headache, dizziness Common

Confusion, drowsiness | Frequency: Uncommon

Depression, psychotic reaction, aseptic meningitis | Frequency: Not known

Clouding of the sensorium | Frequency: Very rare

Cerebrovascular accident* | Frequency: Rare

Ear and labyrinth disorders

Tinnitus, hearing disorders Rare

Eye pathologies

Blurred vision, amblyopia, color vision disorder | Frequency: Rare

Papilloedema | Frequency: Not known

Pathologies of the skin and subcutaneous tissue

Skin rash, skin disease | Frequency: Municipality

Itching, urticaria, purpura, angioedema, rash | Frequency: Uncommon

Bullous dermatoses (erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis), allergic vasculitis | Frequency: Very rare

photosensitivity reactions, aggravation of skin reactions | Frequency: Not known

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) | Frequency: Not known

Acute generalized exanthematous pustulosis (PEAG) | Frequency: Not known

Pathologies of the blood and lymphatic system

Thrombocytopenia, agranulocytosis, aplastic anemia, granulocytopenia, haemolytic anemia | Frequency: Rare

Anemia | Frequency: Not known

Renal and urinary disorders

Hematuria, dysuria | Frequency: Rare

Interstitial nephritis, papillary necrosis, renal failure, acute renal failure | Frequency: Very rare

Hepatobiliary disorders

Hepatotoxicity | Frequency: Rare

Liver damage, hepatitis, jaundice | Frequency: Not known

Diagnostic tests

Liver function test abnormal (transaminases increased), alkaline phosphatase increased, hematocrit decreased, bleeding time prolonged, blood calcium decreased*, uric acid increased* | Frequency: Rare

Decreased hemoglobin level in the blood | Frequency: Very rare

Alteration of renal function tests | Frequency: Not known

Immune system disorders

Allergic reactions | Frequency: Uncommon

Anaphylaxis | Frequency: Rare

Anaphylactic shock | Frequency: Not known

Respiratory, thoracic and mediastinal disorders

Asthma, asthma aggravation, bronchospasm, dyspnoea | Frequency: Uncommon

Throat irritation | Frequency: Not known

Pathologies of the musculoskeletal system and connective tissue

Musculoskeletal stiffness | Frequency: Not known

Metabolism and nutrition disorders

Increased uric acid, sodium and fluid retention or edema | Frequency: Not known

Reproductive system and breast disorders

Menstrual disorder Not known

*effect of the NSAID class The appearance of undesirable effects during treatment requires the immediate suspension of therapy and consultation of the attending physician. Pediatric population From cumulative clinical experience, there is no clinically relevant difference in the nature, frequency, severity and reversibility of adverse reactions between the safety profile in adults and the approved pediatric population (≥12 years). 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 risk/benefit ratio 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.