Naprosyn*os 30bust 250mg

NAME
NAPROSYN

PHARMACOTHERAPEUTIC CATEGORY
Non-steroidal anti-inflammatory and antirheumatic products, derivatives of propionic acid.

ACTIVE PRINCIPLES
Naproxen.

EXCIPIENTS
>> Suppositories: semi-synthetic glycerides. >> Granules 250 mg: sodium chloride; sodium dioctyl sulfosuccinate; povidone; mint flavor; anicement aroma; mannite; sodium saccharinate; sucrose. >> 500 mg granules: mannite; povidone; acrylic resin (Eudragit); sodium saccharinate; lemon flavor; citric acid; precipitated silica; sucrose. >> Modified-release tablets: hypromellose; magnesium stearate; sunset yellow (E110). >> Gastro-resistant tablets: povidone; croscarmellose sodium; magnesium stearate; methacrylic acid copolymer; talc; sodium hydroxide; triethyl citrate; simethicone.

INDICATIONS
Symptomatic treatment of the following conditions: rheumatoid arthritis, osteoarthritis, (degenerative arthritis) ankylosing spondylitis, gouty arthropathy and various forms of extraarticular rheumatism (lumbosciatica, myalgia, neuralgia, root syndromes, periarthritis, fibromyositis).

CONTRAINDICATIONS / SECONDARY EFFECT
Hypersensitivity to the active substance or to other closely related substances from a chemical point of view and / or to any of the excipients.Gastroduodenal ulcer and peptic ulcer in progress. Ulcerative colitis. History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding). Severe heart failure. Patients in whom acetylsalicylic acid and / or other NSAIDs induce allergic manifestations, such as asthma, urticaria, rhinitis, anaphylactic or anaphylactoid reactions and have caused nasal polyps. Children younger than 2 years, as the safety of the product has not been established in this age group. Pregnancy and breastfeeding. Renal insufficiency (creatinine clearance less than 20 ml / min).

DOSAGE
>> Adults. As attack therapy it is recommended to administer 500-1000 mg per day, divided into two doses, at 12 hour intervals (in the morning during breakfast and in the evening during dinner) or in a single administration (during a meal). noon or evening). For this purpose, a modified-release tablet of 750 mg once a day may also be indicated. The dose of 1000 mg (2 x 500 mg) per day in a single administration is recommended: in subjects with severe pain at night and / or with morning stiffness; in patients already unsuccessfully treated with other antirheumatic drugs at high doses; in osteoarthritis when pain is the predominant symptom. As maintenance therapy, depending on the attack dose, the severity of the disease and the painful component, a daily dose of 750-250 mg in a single administration or in two administrations at 12 hours intervals is indicated. In acute gout attacks, a starting dose of 500 mg is recommended, followed by doses of 250 mg every 8 hours for the first 24 hours, subsequently switching to maintenance doses of 250 mg twice daily for 6-7 days. >> Elderly: in such subjects and generally in subjects more 'at risk, the dose must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above. >> Children: the use of the product is not foreseen in pediatric age, except, in the opinion of the doctor in cases of absolute necessity in children over 2 years of age. Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms. >> Hepatic insufficiency: it is advisable to resort to periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment. Such patients should be treated with the lowest effective dose. >> Renal insufficiency: it is advisable to resort to periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment. Chronic treatment is contraindicated in patients with creatinine clearance below 20 ml / minute. The sachets (250 mg and 500 mg), suitably dissolved in water, allow a more rapid absorption of the active substance and perform a quicker analgesic action; they are also more suitable for patients with swallowing difficulties and / or with digestive disorders. The gastro-resistant tablets are a gastroprotected formulation, therefore particularly indicated in all those patients in which dissolution of the drug in the stomach is not recommended; however, its use should be avoided in acute painful states in which prompt analgesic action is required.

STORAGE
It does not require any special storage conditions.

WARNINGS
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms. Particular caution must be adopted in the treatment of patients with severely reduced cardiac, hepatic or renal function. In such patients it is advisable to resort to periodic monitoring of clinical and laboratory parameters, especially in case of prolonged treatment. In particular, chronic treatment is not recommended in patients with creatinine clearance below 20 ml / minute. Patients with impaired liver function should be treated with the lowest effective dose. Elevations of liver function tests may occur as a result of hypersensitivity rather than direct toxicity. Some serious hepatic reactions, including jaundice and hepatitis, some with fatal outcome, have been reported. Caution should be exercised in patients with a history of hypertension and / or heart failure as fluid retention and edema have been reported in association with NSAID therapy. 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. 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. Discontinue at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity '. Use with caution in patients with allergic manifestations in progress or anamnesis as it can cause bronchospasm and other allergic phenomena. Anaphylactic and anaphylactoid reactions may also occur in patients with and without a history of hypersensitivity to aspirin, other NSAIDs or other naproxen-based products. Anaphylactic and anaphylactoid reactions can also occur in subjects with previous angioedema, bronchial reactivity (asthma), rhinitis or nasal polyps. Anaphylactic reactions, as well as anaphylactoids, can be fatal. Bronchospasm can be triggered in patients with previous allergy or asthma, or with hypersensitivity to acetylsalicylic acid. Since ocular alterations have been detected in animal studies with non-steroidal anti-inflammatory drugs, it is recommended that periodic ophthalmological checks be carried out in case of prolonged treatments. Avoid concomitant use of NSAIDs, including selective COX-2 inhibitors. Adequate monitoring and appropriate instructions are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment. Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with naproxen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular events. Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal. Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events. Patients with current or medical history of acute inflammatory gastrointestinal disorders or who have complained of gastrointestinal disorders following other antirheumatic drugs should only undergo treatment under strict supervision. In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing 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. Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment. 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. When gastrointestinal bleeding or ulceration occurs, treatment should be discontinued. Administer with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated. It can decrease platelet aggregation and prolong bleeding time. Caution should be exercised when treating patients with haemostatic disorders or on anticoagulant therapy. Naproxen can decrease fever and inflammation, reducing their usefulness as diagnostic symptoms. The use is not recommended in women intending to become pregnant. Administration should be discontinued in women who have fertility problems or who are undergoing investigation of fertility. The granules for oral suspension contain sucrose.

INTERACTIONS
Since interactions have been observed between non-steroidal anti-inflammatory drugs and highly protein bound drugs, such as hydantoin, sulfonylurea, sulfonamides and coumarin anticoagulants, barbiturates, other NSAIDs and acetylsalicylic acid, they should be observed in order to rule out overdose effects. In patients treated with other non-steroidal anti-inflammatory drugs and with coumarin-type anticoagulants, increased prothrombin time and decreased platelet aggregation have been observed. NSAIDs can increase the effects of blood thinners, such as warfarin. Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding. Corticosteroids: increased risk of gastrointestinal ulceration or bleeding. NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking the product 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 monitoring of renal function should be considered after initiation of concomitant therapy. A decrease in the natriuretic effect of furosemide has been reported following co-administration with some non-steroidal anti-inflammatory drugs. The association of these drugs with lithium leads to a decrease in renal clearance and consequent increase in the plasma concentration of the latter. The medicine may reduce the antihypertensive effect of propanolol and other beta-blockers. Probenecid, when administered simultaneously with the drug, increases its plasma levels and considerably prolongs its half-life. The association with methotrexate should be used with caution as naproxen has been reported to reduce tubular secretion of methotrexate in animal models. It is suggested that therapy be temporarily suspended 48 hours before performing adrenal function tests as it may interfere with some tests for 17-ketogenic steroids. Similarly, the product can interfere with some tests for urinary 5-hydroxyindolacetic acid. Avoid alcohol intake. Naproxen can decrease the effectiveness of intrauterine devices. The use of non-steroidal anti-inflammatory drugs at the same time as quinolone drugs is not recommended. It should not be used at the same time as its salt (naproxen sodium) or vice versa as both circulate in the blood in anionic form. Use at the same time as acetylsalicylic acid or other NSAIDs is not recommended. It can be used simultaneously with gold salts and / or corticosteroids.

SIDE EFFECTS
Blood and lymphatic system disorders: Occasionally, changes such as thrombocytopenia, granulocytopenia, leukopenia, eosinophilia, aplastic or haemolytic anemia have occurred. Alterations of the immune system: anaphylactic or anaphylactoid-type reactions, even serious, may occur in patients with or without previous exposure to drugs belonging to this class. Alterations of metabolism and nutrition: hyperkalaemia. Psychiatric disorders: depression, insomnia, abnormal dreams. Alterations of the nervous system: dizziness, disorientation, retrobulbar optic neuritis, convulsions, headache, somnolence, cognitive dysfunction, difficulty concentrating, aseptic meningitis. Ocular disorders: visual disturbances, corneal opacity, papillitis, papilloedema. Alteration of the auditory system and labyrinth: vertigo, hearing disturbances, ringing in the ears, tinnitus. Cardiac alterations: palpitations, tachycardia, congestive heart failure. Edema, hypertension and heart failure have been reported in association with NSAID treatment. Vascular disorders: hypertension, vasculitis. 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. Alterations of the respiratory system, thorax and mediastinum: dyspnoea, pulmonary edema, asthma, eosinophilic pneumonia, bronchospasm, edema of the larynx. Alterations of the gastrointestinal system: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal, may occur, particularly in the elderly. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal and epigastric pain, heartburn, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease, esophagitis and pancreatitis have been reported. Gastritis was observed less frequently. Alterations of the hepatobiliary system: hepatitis (some cases have been fatal), jaundice. Skin and subcutaneous tissue disorders: rash, pruritus, ecchymosis, urticaria, angioedema, erythema multiforme, erythema nodosum, fixed drug erythema, lichen planus, purpura, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rarely) , photosensitivity reactions, alopecia. Alterations of the musculoskeletal system and connective tissue: myalgia, muscle weakness. Renal and urinary disorders: haematuria, interstitial nephritis, nephrotic syndrome, decreased renal function, renal failure, renal papillary necrosis. Disorders of the reproductive system and of the breast: female infertility. General disorders and administration site alteration: mild peripheral edema, excessive thirst, fever and chills, malaise. Investigations: abnormal liver function test, hypercreatinemia. With the formulation suppositories have also been reported minor local side effects, such as pain and rectal irritation, burning and itching. There have also been isolated cases of rectal haemorrhage, tenesmus and proctitis. However, the incidence of such effects is low.

PREGNANCY AND BREASTFEEDING
It is not recommended for women intending to become pregnant. Administration should be discontinued in women who have fertility problems 'or who are undergoing investigation of fertility'. The product is contraindicated during pregnancy and lactation. Inhibition of prostaglandin synthesis can negatively affect pregnancy and / or embryo / fetal development. Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after 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 believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported. in animals given prostaglandin synthesis inhibitors during the organogenetic period. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose: the fetus cardiopulmonary non-toxicity (with premature closure of the arterial duct and pulmonary hypertension) and / or renal dysfunction, which can progress to renal failure with oligo-hydroamnios; the mother and the newborn, at the end of pregnancy, a possible prolongation of the bleeding time, and an antiplatelet effect that can occur even at very low doses and / or inhibition of uterine contractions resulting in delay or prolongation of labor. The use of the drug in proximity of the delivery determines the delay of the delivery itself; moreover the drug can cause, if administered in this period, alterations to the haemodynamics of the small circulation of the unborn child, with serious consequences for breathing.