Flomax 350 mg 20 sachets granules for oral suspension

In ottemperanza all'articolo 118 “autorizzazione della pubblicità presso il pubblico” del decreto legislativo 24 aprile 2006, numero 219

INDICATIONS

Adults and adolescents over 15 years. Painful and non-painful inflammatory states, even accompanied by fever, affecting the ENT system. (sinusitis, ear infections, tonsillitis, pharyngitis, laryngitis).

ACTIVE INGREDIENTS

FLOMAX 350 mg granules for oral suspension One bipartite sachet contains: Active ingredient: Morniflumate 350 mg. Excipients with known effect: sucrose, sorbitol, aspartame and orange yellow S (E 110). For the full list of excipients, see section 6.1.

EXCIPIENTS

Granulated: Sucrose, Sorbitol, Banana flavour, Maltodextrin, Fruit flavour, Crospovidone, Hypromellose, Aspartame, Ammonium glycyrrhizinate, Xanthan gum, Polysorbate 20, Sodium lauryl sulphate, Orange yellow S (E 110).

CONTRAINDICATIONS AND SIDE EFFECTS

Hypersensitivity to the active substance or to any of the excipients listed in paragraph 6.1; Subjects with gastroduodenal ulcer and subjects with hypersensitivity to the active ingredient or to any of the excipients listed in paragraph 6.1, history of allergy or asthma caused by the administration of niflumic acid/morniflumate or substances with similar activity or closely related from a chemical point of view such as other NSAIDs and aspirin (see paragraph 4.5); 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); Severe hepatic, renal and cardiac insufficiency; Third trimester of pregnancy (see section 4.6); Children and adolescents under 15 years of age. Adolescents with a history of ulcers, rectitis or rectorrhages. The granules (sachets) contain aspartame, therefore they are contraindicated in cases of phenylketonuria.

DOSAGE

Adults and adolescents over 15 years 2 sachets of FLOMAX 350 mg, 2 times a day. Elderly (over 65 years) 1 sachet of FLOMAX 350 mg, 2-3 times a day. In the treatment of elderly patients, the dosage must be carefully established by the doctor who will have to evaluate a possible reduction in the above dosages. The medicine should be used for short-term treatments. The duration of treatment with Flomax should not exceed 5 days. Pediatric population Do not use in children and adolescents under 15 years of age. Method of administration By opening the sachet along the line indicated "full dose" you obtain a dose of 350 mg. FLOMAX must be administered on a full stomach. Side effects can be minimized by using the shortest possible duration of treatment needed to control symptoms (see section 4.4).

CONSERVATION

This medicinal product does not require any special storage conditions.

WARNINGS

Like other NSAIDs, morniflumate can contribute to triggering an asthmatic crisis in patients who have asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis. The administration of morniflumate can cause an asthma attack, particularly in certain subjects allergic to acetylsalicylic acid or an NSAID. Morniflumate may mask the usual signs and symptoms of an infection, therefore it should be used with caution in patients with active infections or in those at risk of infection, even if well controlled. Exceptionally, chickenpox can cause serious infectious complications of the skin and soft tissues. At the moment it cannot be excluded that NSAIDs may favor the worsening of these infections. Consequently, it is advisable to avoid the use of morniflumate in case of chickenpox (see section 4.8). During prolonged treatments, periodic blood count tests and liver and kidney function tests are advisable. Precautions for use Urinary volume and renal function must be strictly monitored at the beginning of treatment with morniflumate in patients with chronic heart failure, renal or hepatic failure, taking diuretics, who have undergone major surgery with consequent hypovolemia, and in particular in elderly subjects. The use of FLOMAX should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors. 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 sections below on gastrointestinal and cardiovascular risks). Cardiovascular and cerebrovascular effects 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 and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There are insufficient data to exclude a similar risk for morniflumate. Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with morniflumate only after careful consideration. Similar considerations must be made before starting long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking). Gastrointestinal bleeding, 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. The relative risk increases in the elderly, in debilitated subjects, in people with low body weight and in patients undergoing therapy with anticoagulants or antiplatelet agents. When gastrointestinal bleeding or ulceration occurs in patients taking FLOMAX, treatment should be discontinued. NSAIDs should be administered with caution and under close medical supervision in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease, hiatal hernia) since these conditions may be exacerbated (see section 4.8 Undesirable effects). 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). Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2). 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) 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 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. Skin effects Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, 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. FLOMAX should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Interference with laboratory analyses In subjects treated with niflumic acid or morniflumate, false-positive results in the immunoassay test for the presence of cannabinoids in urine have been reported (see section 4.8). Further analyzes are required to confirm the positive result. Pediatric population As with other NSAIDs, the use of morniflumate in pediatrics should be carried out after careful evaluation of the risk-benefit ratio for each individual patient. When treating pediatric patients, it is advisable to strictly adhere to the recommended posology (see paragraph 4.2), avoiding therapeutic combinations that could increase the risk of possible adverse reactions. Literature data suggest that the use of niflumic acid in the pediatric population could be associated with an increased risk of serious mucocutaneous reactions. The granules (sachets) contain sucrose: patients suffering from rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine; take this into account when administering to diabetic patients and those undergoing low-calorie diets. The granules also contain sorbitol: patients suffering from rare hereditary problems of fructose intolerance should not take this medicine; can cause gastric problems and diarrhea. The use of FLOMAX, as with any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women intending to become pregnant.

INTERACTIONS

Diuretics, ACE inhibitors and angiotensin II antagonists 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) 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 morniflumate 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. Risk linked to hyperkalemia Some medicinal products or therapeutic classes can favor the onset of hyperkalemia: potassium salts, diuretics, ACE (angiotensin converting enzyme) inhibitors, angiotensin II inhibitors, NSAIDs, heparins (both low molecular weight and unfractionated), ciclosporin, tacrolimus and trimethoprim. The onset of hyperkalemia may depend on the existence of associated factors. This risk increases when there is a combination with the medicinal products mentioned above. Risk linked to the anti-aggregating effect Many substances are involved in interactions due to their antiaggregating properties: aspirin and NSAIDs, ticlopidine and clopidogrel, Tirofiban, eptifibatide and abciximab, iloprost. The use of many antiplatelet agents increases the risk of bleeding as does their combination with heparins, oral anticoagulants and thrombolytics. Such use must be subject to regular clinical and biological control. Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal haemorrhage (see section 4.4). Anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin (see section 4.4). Corticosteroids: increased risk of gastrointestinal ulceration or haemorrhage (see section 4.4). The simultaneous administration of morniflumate with the following products requires close clinical and biological control of the patient. Combinations not recommended With other NSAIDs (including acetylsalicylic acid and other salicylates) An increased risk of gastrointestinal ulcers and haemorrhages has been found (additive synergy). With other anticoagulants An increased risk of bleeding (inhibition of platelet function and damage to the gastroduodenal mucosa caused by NSAIDs) has been found. If this combination cannot be avoided, close clinical and laboratory monitoring of the patient is required. With heparin at curative doses or in elderly patients An increased risk of haemorrhage has been found (inhibition of platelet function and irritation of the gastroduodenal mucosa caused by NSAIDs). If this combination cannot be avoided, close clinical and laboratory monitoring of the patient is required. NSAIDs should be administered for a few days. With lithium Lithium levels in the blood are increased and toxic concentrations can be reached (reduced renal excretion of lithium). Where necessary, blood lithium levels should be closely monitored and the lithium dosage adjusted during combination treatment and after NSAID treatment has been discontinued. With methotrexate, used at higher doses of 15 mg per week An increased risk of haematological toxicity caused by methotrexate has been found (anti-inflammatories reduce the renal clearance of methotrexate). Combinations that require precautions for use With diuretics, ACE inhibitors, and angiotensin II inhibitors Acute renal failure has been found in patients at risk (elderly and/or dehydrated subjects) due to a decrease in glomerular filtration (NSAIDs inhibit vasodilatory prostaglandins). Rehydrate the patient. At the beginning of treatment, renal function should be checked. With methotrexate used at doses less than 15 mg per week An increased risk of haematological toxicity caused by methotrexate has been found (anti-inflammatories reduce the renal clearance of methotrexate). Haematological counts should be monitored weekly during the first few weeks of combination treatment. If renal insufficiency occurs (even if mild), and in elderly patients, close monitoring is required. Combinations that need to be taken into consideration An increased risk of bleeding has been found with other antiplatelet agents (ticlopidine, clopidogrel, Tirofiban, eptifibatide and abciximab, iloprost) and with heparins at prophylactic doses. An increased risk of hyperkalaemia has been found with other agents causing hyperkalaemia (potassium salts, potassium-sparing diuretics, ACE (angiotensin converting enzyme) inhibitors, angiotensin II inhibitors, other NSAIDs, heparins (both low molecular weight and unfractionated), ciclosporin, tacrolimus and trimethoprim. With beta blockers (by extrapolation of indomethacin data) A reduction in the antihypertensive effect has been found (NSAIDs inhibit vasodilatory prostaglandins). With cyclosporine Risk of potentiation of nephrotoxic effects, particularly in elderly patients.

SIDE EFFECTS

The adverse events most commonly observed with NSAIDs are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4). Edema, hypertension and heart failure have been reported in association with NSAID treatment. The frequency of adverse events, reported in the table below, cannot be defined on the basis of the available data, as they were reported during the post-marketing experience.

Infections and infestations(*) - Adverse reaction: Worsening of skin infections (in the presence of chickenpox, see paragraph 4.4).

Blood and lymphatic system disorders - Adverse reaction: Thrombocytopenia, leukopenia.

Immune system disorders - Adverse reaction: Anaphylactic shock.

Nervous system disorders - Adverse reaction: Headache, dizziness.

Cardiovascular disorders - Adverse reaction: Myocardial infarction or cerebrovascular accident (see section 4.4)**, edema, hypertension and heart failure, hypotension, vasculitis,.

Respiratory, thoracic and mediastinal disorders - Adverse reaction: Asthmatic crisis (especially in patients allergic to acetylsalicylic acid or other NSAIDs).

Gastrointestinal disorders(*) - Adverse reaction: Peptic ulcer, gastrointestinal perforation, gastrointestinal haemorrhage (sometimes fatal, particularly in the elderly, see section 4.4), nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, epigastralgia, melena, haematemesis, ulcerative stomatitis, gastrointestinal ulcers (with or without haemorrhage), haemorrhagic colitis, exacerbation of colitis and Crohn's disease, gastritis.

Skin and subcutaneous tissue disorders - Adverse reaction: Rash, urticaria, purpura, pruritus, erythema multiforme, erythema multiforme and dermatitis, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis, photosensitization dermatitis, angioedema of the face, tongue, eyelids, lips, larynx, pharynx.

Renal and urinary disorders - Adverse reaction: Acute renal failure, tubulointerstitial nephritis, nephrotic syndrome, hematuria.

Injury, poisoning and procedural complications - Adverse reaction: Fluorosis (at high doses for several years).

Diagnostic tests - Adverse reaction: Abnormal liver function tests, false positive urine test result for cannabinoids (see section 4.4).

(*) Increases in the dosage and duration of treatment influence the increase in the frequency of gastrointestinal side effects (see section 4.4). In case of chickenpox, serious infectious skin complications may occur (see section 4.4). (**)Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with a modest increase in the risk of arterial thrombotic events (i.e. myocardial infarction or cerebrovascular accident; see section 4.4). Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. 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.

OVERDOSE

In the case of overdose with niflumic acid/morniflumate the predictable symptoms are: gastrointestinal irritation, drowsiness (5%) and headache. A subject who ingested 7.5 g of niflumic acid showed glomerulonephritis, which resolved without sequelae. In case of overdose, symptomatic treatment is indicated, in addition to gastric lavage and the administration of activated charcoal (oral forms only).

PREGNANCY AND BREASTFEEDING

Fertility. Cases of secondary non-ovulatory infertility caused by failure of the Graafian follicle to rupture have been reported in patients of childbearing age taking prostaglandin synthesis inhibitors as long-term treatment. This infertility is reversible upon discontinuation of treatment. Pregnancy. Inhibition of prostaglandin synthesis can 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 the early stages of 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. From the 20th week of pregnancy onwards, the use of FLOMAX may cause oligohydramnios resulting from fetal renal dysfunction. This condition may be experienced shortly after starting treatment and is usually reversible upon discontinuation of treatment. Additionally, cases of constriction of the ductus arteriosus have been reported following treatment in the second trimester, most of which resolved after treatment was discontinued. Therefore, during the first and second trimester of pregnancy, FLOMAX should not be administered unless strictly necessary. If FLOMAX is used by a woman planning to become pregnant, or during the first and second trimester of pregnancy, the lowest possible dose should be used for the shortest possible time. Following exposure to FLOMAX for several days from 20 weeks of gestation onwards, antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered. In case of oligohydramnios or constriction of the ductus arteriosus, treatment with FLOMAX must be discontinued. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to: - cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension), - renal dysfunction (see above); 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 delay or prolongation of labour. Consequently, FLOMAX is contraindicated during the third trimester of pregnancy (see sections 4.3 and 5.3). Breastfeeding. The concentration of niflumic acid/morniflumate in milk is low. However, as a precaution, breastfeeding should be discontinued.

EFFECTS ON DRIVING ABILITY

Similar to other non-steroidal anti-inflammatory drugs, the drug could induce drowsiness or sensory dullness with impairment of activities that require quick reflexes (driving motor vehicles, using machinery, etc.). The patient should be advised of the possibility of manifestations such as dizziness or drowsiness.