LISINA ZEN 12BS

KETOPROFENE SALE DI LISINA ZENTIVA ITALY 40 G FREE

active ingredients

A bag contains: Active ingredient : ketoprofen salt of lysine 40 mg (corresponding to 25 mg of ketoprofene) Excipient with known effects: aspartame. For the full list of excipients, see paragraph 6.1.

Excellent

Mannitol, xylitol, lime aroma, lemon aroma, fresh aromafort, aspartame, talc, basic butylated methacrylate copolymer, magnesium stearate, colloidal silica moisturizes, ipromellosa, stearic acid, povidone, sodium laurilsolfato.

Therapeutic indications

Syntomatic treatment of mild and moderate acute pain.

Contraindications

Ketoprofene salt of lisina Zentiva Italy should not be administered in the following cases: • hypersensitivity to the active ingredient, other non-steroidal anti-inflammatory drugs (NSAID) or any of the excipients listed in the paragraph 6.1. • patients with positive anamnesis for hypersensitivity reactions, such as bronchospasm, asthma attacks, acute rhinitis, nasal polyps, urticaria, angioneurotic edema or other allergic reactions to ketoprofen or substances with similar mechanism of action [per esempio acido acetilsalicilico (ASA) o ad altri farmaci antinfiammatori non steroidei (FANS)]. Serious, rarely fatal anaphylactic reactions were reported in these patients (see paragraph 4.8). • peptic ulcer/active hemorrhage, or earlier gastrointestinal hemorrhage anamnestics, ulceration or perforation (two or more distinct episodes, proven by bleeding or ulceration) or chronic dyspepsia. • gastrointestinal bleeding or gastrointestinal perforation resulting in previous therapy with NSAIDs or other active bleeding or hemorrhagic disorders. • severe heart failure. • severe liver failure. • severe kidney failure. • hemorrhagic diathesis and other clotting disorders, or patients with anticoagulant therapy. • patients subjected to important surgery. • third trimester of pregnancy and nursing (see paragraph 4.6) • children and adolescents under the age of 15.

Population

Population Adults and teenagers over 15 years: 1 sachet, in single dose, or repeated 2-3 times a day, in painful forms of greater intensity. The duration of therapy must be limited to overcoming the painful episode (see paragraph 4.4). The lowest effective dose should be used for the shortest period necessary to relieve symptoms (see paragraph 4.4). Special popularity Seniors: elderly patients must comply with the above minimum dosages. Patients with mild or moderate renal impairment: it is recommended to monitor diuresis volume and kidney function (see paragraph 4.4). Patients with mild or moderate liver failure: must be followed carefully and treated with the minimum effective daily dose (see paragraph 4.4). Ketoprofene salt of lisin Zentiva Italy should not be used in patients with severe liver and kidney dysfunction (see paragraph 4.3). Pediatric population Ketoprofene salt of lisina Zentiva Italy is contraindicated in children and adolescents under the age of 15. Method of administration The contents of the sachet can be placed directly on the tongue. It dissolves with saliva: this allows the use without water. It is preferable to take the medicine on a full stomach.

Conservation

This medicine does not require any special precaution for conservation.

Warnings

Carefully administer in patients with allergic manifestations or pregress allergy. Treatment with ketoprofen salt of lysine must be stopped at the first appearance of skin rash, mucosa lesions or any other sign of hypersensitivity. Undesirable effects can be minimized with the use of the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see paragraph 4.2 and below paragraphs on gastrointestinal and cardiovascular risks). The concomitant use of Ketoprofene salts of lisin Zentiva Italy with other NSAIDs, including selective inhibitors of cyclooxygenase-2, must be avoided (see paragraph 4.5). Senior patients have an increased frequency of adverse reactions to NSAIDs, especially hemorrhages and gastrointestinal perforations, which can be fatal. As with other NSAIDs, in the presence of an infection, it is necessary to consider that the anti-inflammatory, analgesic and antipyretic properties of ketoprofen can mask the common symptoms of progression of infection such as fever. Cardiovascular and cerebrovascular effects Adequate monitoring and appropriate instructions are necessary in patients with positive anamnesiums for hypertension and/or mild to moderate congestive heart failure, as fluid, hypertension and edema were observed in combination with NSAID treatment. Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially high doses and long-term treatments) may be associated with a modest increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There is not enough data to exclude a similar risk for ketoprofen salt of lysine when it is given to the daily dose of a sachet, in single dose, or repeated 2-3 times a day. Patients with uncontrolled hypertension, congestive heart failure, established ischemic cardiopathy, peripheral arterial disease and/or cerebrovascular disease must be treated with ketoprofen salt of lisina, as well as with all NSAIDs, only after careful evaluation. Analogue considerations must be made before starting a long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking). Gastrointestinal effects During treatment with all NSAIDs, at any time, with or without warning symptoms or previous history of serious gastrointestinal events, gastrointestinal hemorrhage, ulceration and perforation, which may be fatal. Some epidemiological evidence suggests that ketoprofen salt of lysine can be associated with a high risk of severe gastrointestinal toxicity, compared to other NSAIDs, especially at high doses. In the elderly and in patients with history of ulcer, especially if complicated by hemorrhage or perforation (see paragraph 4.3), the risk of gastrointestinal hemorrhage, ulceration or perforation is higher with increased doses of NSAID. These patients must begin treatment with the lowest dose available. Concurrent use of protective agents (misoprostol or protonic 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 paragraph 4.5). Patients with history of gastrointestinal toxicity, especially elderly, must report any unusual gastrointestinal symptoms (especially gastrointestinal hemorrhage) in particular in the early stages of treatment. Caute should be lent to patients taking concomitant drugs that may increase the risk of ulceration or hemorrhage, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-aggregating agents such as aspirin (see paragraph 4.5). When hemorrhage or gastrointestinal ulcer occurs in patients taking Ketoprofene salt of lysine treatment should be suspended. NSAIDs should be given with caution in patients with a history of gastrointestinal disease ( ulcerative colitis, Crohn's disease) since such conditions can be exacerbated (see paragraph 4.8). Effects on the skin Severe skin reactions some of which fatal, including exfoliative dermatitis, Stevens- Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see paragraph 4.8). In the early stages of therapy patients seem to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Ketoprofen salt of lysine must be stopped at the first appearance of skin rash, mucosa lesions or any other sign of hypersensitivity. Kidney and hepatitis effects As with all NSAIDs, the drug can increase plasma urethic nitrogen and creatinine. As with other prostaglandin synthesis inhibitors, ketoprofene salt of lysine can be associated with adverse events on the kidney system that can lead to glomerular nephritis, kidney papillar necrosis, nephrosic syndrome and acute kidney failure. It should be carefully monitored the kidney function at the beginning of treatment in patients with heart failure, with cirrhosis and nephrosis, in patients in diuretic therapy, with chronic kidney failure especially if elderly. In such patients the administration of ketoprofen salt of lysine can cause a reduction of kidney blood flow, caused by the inhibition of prostaglandins and lead to kidney alterations. As with other NSAIDs, the drug may cause small transient increments in certain hepatic parameters and also significant increases in SGOT and SGPT (see paragraph 4.8). In the event of a significant increase in these parameters, therapy must be interrupted. In patients with impaired liver function or with previous liver disease, transaminers should be regularly assessed particularly during long-term therapy. With ketoprofen salt of lysine were reported cases of jaundice and hepatitis. When administering ketoprofen salt of lysine in patients with liver porphyria it is required attention since it could trigger an attack. Ketoprofene salt of lysine must be administered with caution in patients suffering from hematopoietic alterations, systemic lupus erythematomatous or mixed affections of connective tissue. The use of NSAIDs can compromise fertility and is not recommended in women who want to start a pregnancy (see paragraph 4.6). The administration of ketoprofen should be suspended in women who have difficulty in conceiving or who are subject to fertility surveys. Treatment should be interrupted in case of appearance of visual disturbances such as blurred vision. Patients who have asthma associated with chronic rhinitis and allergy, chronic sinusitis and/or nasal polyposes have a higher risk of aspirin and/or NSAID allergy than the rest of the population. The administration of this medicine may cause asthma or bronchospasm attacks, especially in acetylicylic acid (aspirin) or NSAIDs (see paragraphs 4.3 and 4.8). Therefore in these subjects, as well as in the case of chronic obstructive bronchopathy or nephropathy, the medicinal product should only be used under medical supervision. To avoid any hypersensitivity or photosensitization phenomena, it is advisable not to expose yourself to the sun during use. Masking the symptoms of underlying infections Ketoprofen Lysine Salt can mask the symptoms of infection, which may delay the start of appropriate treatment and thus worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When Ketoprofen Lysine Salt is administered for 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. Important information about some excipients Ketoprofene salt of lysine Zentiva Italy contains 10,56 mg of aspartame per dose (1 sachet) equivalent to 31,78 mg per recommended daily maximum dose (3 sachets). Aspartame is a source of phenylalanine. It can be harmful in patients with phenylchetonuria.

Interactions

Not recommended associations • Other NSAIDs (including selective cycloxygenase-2 inhibitors), including high doses salicylates (≥ 3g/die): the simultaneous administration of several NSAIDs can increase the risk of gastrointestinal ulcers and bleeding, due to a synergistic effect. • Antiagulants (e.g. heparine and warfarin) and anti-aggregating agents (e.g ticlopidine and chlopidogrel): increased risk of bleeding by inhibiting pyasternic function and giving gastrointestinal mucosa (see paragraph 4.4). If concurrent administration cannot be avoided, patients must be carefully monitored. • Litio: risk of increased plasma levels of lithium, which can sometimes reach toxic levels due to reduced renal excretion of lithium. Where necessary, the plasma levels of lithium must be carefully monitored with possible adjustment of the dosage during and after therapy with NSAIDs. • Metotrexate, used at high doses, (superior at 15 mg/week): increased risk of blood toxicity of metotrexate, especially when administered at high doses (>15 mg/week), probably due to the displacement of metotrexate from protein bond and the reduction of its kidney clearance. • Idantoine and sulphuramides: the toxic effects of these substances can be increased. Associations requiring precaution • Courtesy: increased risk of gastrointestinal ulceration or bleeding (see paragraph 4.4). • Diuretics: patients taking diuretics, especially if dehydrated, are at high risk of developing secondary kidney failure to reduce kidney blood flow caused by prostaglandin inhibition. Patients should be properly hydrated and monitoring of renal function must be taken into account after the start of concomitant therapy (see paragraph 4.4). NSAIDs can reduce the effect of diuretics. Concurrent use of NSAIDs and potassium-saving diuretics, as well as a reduction in diuretic effect and potential nephrotoxicity, can also lead to hyperpotassium. • ACE inhibitors and angiotensin antagonists II: in some patients with impaired kidney function (e.g. dehydrated patients or elderly patients with impaired kidney function) co-administration of an ACE inhibitor or an antagonist of angiotensin II and agents that inhibit the cycloxygenase system can lead to further deterioration of kidney function, with possible occurrence of acute kidney failure. The combination should therefore be given with caution, especially in elderly patients. Patients should be properly hydrated and monitoring of renal function should be taken into consideration after the start of concomitant therapy. • Metotrexate used at low doses, less than 15 mg/week: during the first weeks of the combined therapy, an emochromocytometric examination must be carried out every week. In the presence of a slight worsening of kidney function or in older patients, monitoring must be more frequent. • Pentoxyphylline: increased risk of bleeding. It is necessary to increase clinical monitoring and more frequently control bleeding time. • Zidovudina: risk of increased toxicity on the red cell line by action on the reticulocytes, with severe anemia manifesting a week after the start of treatment with the NSAID. Check the full hemocytometric examination and count of reticulocytes one or two weeks after starting treatment with the NSAID. • Tenofovir: concurrent administration of tenofovir disoproxyl fumarate and FANS may increase the risk of kidney failure. • Sulfaniluree: NSAIDs can increase the hypoglycemic effect of sulfaniluree by spying on them from the linked sites with plasma proteins. Associations that need to be considered: • Antihypertensives (beta-blockers, angiotensin converting enzyme inhibitors, diuretics): NSAIDs can reduce the effect of antihypertensive drugs by inhibiting the synthesis of prostaglandins Trombolites: increased risk of bleeding. • Probenecid: concomitant administration of probenecid may significantly reduce the plasma clearance of ketoprofen and consequently plasma concentrations of ketoprofen may be increased;this interaction may be due to an inhibitory mechanism at the site of renal tubular secretion and glucuronide conjugation and requires an adaptation of the ketoprofen dose Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants: increased risk of gastrointestinal and intracranial hemorrhage (see paragraph 4.4). • Cyclosporine, tacrolimus: risk of nephrotoxic additive effects, particularly in older people. During associated therapy, kidney function must be measured. • Chinolonic Antibiotics: animal data indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics.Patients taking NSAIDs and quinolones may be at increased risk of developing seizures.

Effects

The most commonly observed adverse events are gastrointestinal. Peptic ulcers, perforation or gastrointestinal hemorrhage may occur, sometimes fatal, especially in the elderly (see paragraph 4.4). The frequency and extent of these effects are reduced by taking full stomach medicine. The manifestations of hypersensitivity can assume the character of severe systemic reactions (edema of the larynx, edema of the glottis, dispnea, palptation) up to the anaphylactic shock. In these cases immediate medical care is required. The following adverse reactions were observed following the administration of ketoprofen salt of lysine in adults. The frequency of adverse events is classified as follows: very common (≥1/10); common (≥1/100, Infections and infestations Not known: aseptic meningitis, lymphangitis. Emolinfopoietic system pathologies: Rare: Hemorrhagic anemia. Notable: agranulocytosis, thrombocytopenia, midollar aplasia, hemolytic anemia, leukopenia, neutropenia, aplastic anemia, leukocytosis, thrombocytopenic purple. Immune system disorders: Not known: anaphylactic reactions (including shock), hypersensitivity. Psychiatric disorders: Not known: depression, hallucinations, mood alteration, excitability, insomnia. Diseases of the nervous system: Not common: headache, dizziness, drowsiness. Rare: parestesia. Notable: syncope, convulsions, dysgeusia, tremor, hypercinesia, dyskinesia, dizziness. Pathologies of the eye: Rare: blurred vision (see paragraph 4.4). Notable: Periorbital edema. Ear and labyrinth disorders: Rare: Tinnitus. Heart disease: Notable: heart failure, palpitations, tachycardia. Vascular diseases: Not known: hypotension, hypertension, vasodilation, vasculitis.Respiratory, chest and mediastinic pathologies: Rare: asthma. Notable: edema of larynx, bronchospasm (especially in patients with hypersensitivity known to acetylsalicylic acid and other NSAIDs), rhinitis, dispnea, larynxospasm, acute respiratory failure. Gastrointestinal diseases: Common: nausea, vomiting, dyspepsia, abdominal pain. Not common: constipation, diarrhea, flatulence, gastritis. Rare: ulcerative stomatitis, peptic ulcer. Do not note: exacerbation of colitis and Crohn's disease, gastrointestinal hemorrhage and perforation (see paragraph 4.4), gastric ulcer, duodenal ulcer, pancreatitis, melena, ematemesis, gastric pain, erosive gastritis, edema of the tongue. Hepatobiliary diseases: Rare: hepatitis, increased serum levels of transaminers, high levels of serum bilirubin due to hepatitis, jaundice. Pathologies of skin and subcutaneous tissue: Not common: rash, itching. Notable: photosensitization, alopecia, hives, angioedema, bollose eruptions, including Stevens-Johnson syndrome, Lyell syndrome, and epidermal toxic necrolysis, erythema, esantema, maculo-papulare esantema, porpora, dermatitis. Kidney and urinary pathologies: Notable: water retention, hematuria, acute kidney failure, piping-interstitial nephritis, nephritic syndrome, glomerular nephritis, acute tubular necrosis, kidney papillar necrosis, nephrosic syndrome, oliguria, abnormality in kidney function tests, disuria. Systemic pathologies and conditions for administration: Not common: edema, fatigue. Not known: bruises, asthenia, facial edema, peripheral edema. Diagnostic examinations: Rare: weight gain. 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 the address www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

Overdosing

Overdose cases were reported with doses greater than 2.5 g of ketoprofene salt of lysine. In most cases, observed symptoms include: lethargy, drowsiness, nausea, vomiting and epigastric pain. Overdose symptoms may also include: central nervous system disorders, such as headaches, dizziness, confusion and loss of consciousness. Hypotension, respiratory depression and cyanosis may occur. Renal failure, convulsions and coma have also been described. A single case of anxiety, visual hallucinations, hypereccitability and alteration of behavior was reported in a pediatric patient who had taken a double dose compared to the recommended one. Symptoms disappeared spontaneously within 1-2 days. There are no specific antidotes for an overdose of ketoprofene salt of lysine. In the event of a suspicion of severe overdose, gastric lavender and the establishment of supporting and symptomatic therapies to compensate for dehydration, to monitor renal function and to correct acidosis if present. In case of kidney failure, hemodilysis may be useful for removing the drug from the circle.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development.Results of epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy.The absolute risk for cardiac malformation increased from less than 1%, up 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 result in increased pre- and post-implantation loss, embryo-foetal mortality and an increased incidence of various malformations, including cardiovascular (see section 5.3).Therefore, ketoprofen should not be administered during the first and second trimester of pregnancy unless clearly necessary.If ketoprofen is used in women attempting 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 prostaglandin synthesis inhibitors may 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 oligo-hydroamniosis;the mother and the neonate, at the end of pregnancy, to: • possible prolongation of bleeding time, and anti-aggregating effect which may occur even at very low doses;• inhibition of uterine contractions resulting in delayed or prolonged labor.Ketoprofene lysine salt Zentiva Italia is therefore contraindicated during the third trimester of pregnancy.

Food

Since no data is available on the secretion of ketoprofen salt of lysine in breast milk, ketoprofene should not be given during breastfeeding.

Fertility

The use of ketoprofen salts of lysine, as of any inhibitor drug of the synthesis of prostaglandins and cycloxygenase is not recommended in women who intend to start a pregnancy. The administration of ketoprofen salt of lysine must be suspended in women who have fertility problems or who are subject to fertility surveys.

Source: Farmadati