KETODOL 20CPR 25MG+200MG

KETODOL 25 MG + 200 MG COMPRESENT

active ingredients

One tablet contains: Active ingredients: Core: ketoprofen 25 mg; Coating: sucralfate 200 mg. Excipients with known effects: contains lactose and sodium. For the full list of excipients, see paragraph 6.1.

Excellent

Core: lactose monohydrate, carbossimetilamido sodium (type A), povidone, magnesium stearate. Coating: maize starch, sodium starch glycolate (type A), povidone, talc, magnesium stearate, cochineal red (E120).

Therapeutic indications

Pain of various origins and natures (headache, toothache, neuralgia, osteo-articular and muscular pain, menstrual pain).

Contraindications

KETODOL is contraindicated in patients with a history of hypersensitivity reactions, such as bronchospasm, asthmatic attacks, rhinitis, urticaria or other allergic-type reactions, to ketoprofen, acetylsalicylic acid (ASA) or other nonsteroidal anti-inflammatory drugs (NSAIDs).Serious, rarely fatal, anaphylactic reactions have been reported in these patients (see section 4.8). KETODOL It is also contraindicated in the following cases: - hypersensitivity to the active substances or to any of the excipients listed in paragraph 6.1;- during intensive diuretic therapy;- chronic dyspepsia;- gastritis;- severe renal insufficiency;- severe forms of liver insufficiency (liver cirrhosis, severe hepatitis);- porphyria, leukopenia and thrombocytopenia;- subjects with active haemorrhages;- haemorrhagic diathesis;- subjects with haemostatic disorders;- severe cardiac insufficiency;- active peptic ulcer or previous history of gastrointestinal haemorrhage, ulceration or perforation;- history of gastrointestinal bleeding or perforation resulting from previous therapy with NSAIDs;- do not administer during antibiotic treatments with tetracyclines to avoid the formation of complex salts with inactivation of the antibiotic itself on contact with sucralfate. KETODOL It is also contraindicated during the third trimester of pregnancy, during breastfeeding (see paragraph 4.6) and in paediatric age.

Dosage

Adults and children over 15 years: 1 tablet in a single dose or repeated 2 - 3 times a day, in the most intense painful forms.It is preferable to take the product on a full stomach (with a glass of water).Do not exceed the recommended doses: elderly patients in particular should stick to the minimum doses indicated above.The duration of therapy should be limited to overcoming the painful episode.The lowest effective dose should be used for the shortest period necessary to relieve the symptoms (see paragraph 4.4.) Special populations Patients with renal insufficiency and the elderly: It is recommended to reduce the initial dose and perform maintenance therapy with the minimum effective dose.Individualized adjustments can be considered only after establishing good tolerability of the drug (see paragraph 5.2). Patients with hepatic impairment: Patients with mild or moderate liver failure must be followed carefully and treated with the minimum effective daily dose (see paragraphs 4.3, 4.4 and 5.2). Pediatric population: The safety and efficacy of ketoprofen have not been studied in children.

Conservation

This medicinal product does not require any special storage conditions

Warnings

Warnings: Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2 and following paragraphs).Concomitant use of KETODOL with other NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided. Gastrointestinal bleeding, ulceration and perforation: 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. 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 the elderly, must report any abdominal symptoms (especially gastrointestinal hemorrhage) in particular in the early stages of treatment. Caute should be lent to patients taking concomitant drugs that could 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 bleeding or gastrointestinal ulcer occurs in patients taking KETODOL treatment must be suspended immediately. 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). Some epidemiological evidence suggests that ketoprofen may be associated with a high risk of severe gastrointestinal toxicity, compared to other NSAIDs, especially at high doses (see paragraphs 4.2 and 4.3). Seniors: Senior patients have an increased frequency of adverse reactions to NSAIDs, especially hemorrhages and gastrointestinal perforations, which can be fatal (see paragraph 4.2). Skin reactions: 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 reaction occurs in most cases within the first month of treatment. KETODOL must be stopped at the first appearance of skin rash, mucosa lesions or any other sign of hypersensitivity. To avoid any hypersensitivity or photosensitization phenomena, it is advisable not to expose yourself to the sun during use. Precautions. Cardiovascular, kidney and liver dysfunction: 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 can cause a reduction in kidney blood flow, caused by the inhibition of prostaglandins and lead to a renal breakdown (see paragraph 4.3 Contraindications). In patients with impaired liver function tests or with previous liver disease, transaminers should be regularly assessed particularly during long-term therapy. With ketoprofen cases of jaundice and hepatitis were reported. The product, like all non-steroidal anti-inflammatory drugs, interferes with the synthesis of prostaglandins and their important intermediates that are part of physiological functions. The drug, therefore, requires special precautions, or imposes its exclusion from use, when the patient has the following conditions: kidney hypoperfusion states, kidney disease, heart failure, mild to moderate liver failure, advanced age. Cardiovascular and cerebrovascular effects: Cautisus is required in patients with positive anamnesis for hypertension and/or congestive heart failure from mild to moderate because in association with the treatment with the NSAIDs, fluid retention and edema were found. Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially high dosages and long-term treatments) may be associated with an increase in the risk of arterial thrombotic events (p.es. infarction of myocardial or stroke). There is not enough data to exclude a similar risk for ketoprofen. Patients with uncontrolled hypertension, congestive heart failure, established ischemic cardiopathy, peripheral arterial disease and/or cerebrovascular disease should be treated with ketoprofen 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). An increase in the risk of atrial fibrillation associated with the use of NSAIDs has been reported. Hyperpotassemia may occur, especially in patients with underlying diabetes, kidney failure, and/or concomitant treatment with hyperpotassemia promoters (see paragraph 4.5). Under these circumstances, potassium levels must be monitored. Masking the symptoms of underlying infections: KETODOL may mask the symptoms of infection, which may delay the start of proper treatment and thus worsen the outcome of the infection. This was observed in bacterial pneumonia acquired in communities and bacterial complications of chickenpox. When KETODOL is administered for relief from fever or pain related to infection, it is recommended to monitor the infection. In non-hospital contexts, the patient should contact the doctor if symptoms persist or worsen. Respiratory diseases: Patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyps have a higher risk of aspirin allergies and/or NSAIDs than the rest of the population. The administration of this medicine may cause asthma or bronchospasm attacks, particularly in aspirin or NSAIDs (see paragraph 4.3). For the interaction of the drug with the metabolism of arachidonic acid, in asthmatics and predisposed subjects can arise bronchospasm crisis and possibly shock and other allergic phenomena. Visual disturbances: If you experience vision disorders as blurred vision the treatment should be stopped. The use of ketoprofen, as of any drug inhibitor of the synthesis of prostaglandins and cyclooxygenase, is not recommended in women who intend to start a pregnancy. The administration of ketoprofen should be suspended in women who have fertility problems or who are subject to fertility surveys. The bioavailability of other drugs may be altered, so a range of at least two hours between the intake of the product and that of other medicine will be interrupted. For these reasons it is appropriate for patients subjected to any other treatment to consult the doctor before taking the product. Cases of bezoar formation were reported associated with the administration of sucralfate. Most of these were patients in intensive care. Therefore, extreme caution must be exercised in the treatment of patients in intensive care especially if they receive enteral nutrition, or in patients who present predisposable factors as delayed gastric emptying. After three days of treatment without appreciable results, consult your doctor. Important information about some excipients: This medicine contains lactose: patients with rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose mal absorption, should not take this medicine. This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘without sodium’.

Interactions

UNCONSOLIDATED ASSOCIATIONS Other non-steroidal anti-inflammatory drugs (including selective cycloxygenase-2 inhibitors) and high dose salicylates: it is appropriate not to associate KETODOL with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (including selective cyclooxygenase-2 inhibitors): increased risk of ulcers and gastroenteric bleeding. Antiagulants (heparin and warfarin) and anti-aggregating agents (e.g. ticlopidine, chlopidogrel): increased risk of bleeding (see paragraph 4.4). NSAIDs can amplify the effects of anticoagulants as warfarin. If it is not possible to avoid concurrent administration, patients must be followed carefully. 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 should be monitored with possible adjustment of the dosage during and after therapy with NSAIDs. Metotrexate at doses greater than 15 mg/week: increased risk of hematological toxicity by metotrexate, especially when administered at high doses (> 15 mg/week), probably due to displacement of metotrexate by protein bond and reduced kidney clearance. In patients already in treatment with ketoprofen it is necessary to stop therapy at least 12 hours before the administration of metotrexate. If ketoprofen should be administered at the end of metotrexate therapy, it is necessary to wait 12 hours before administration. ASSOCIATIONS REQUEST CAUTEL Drugs or therapeutic categories that can promote hyperpotassemia (e.g. potassium salts, potassium-saving diuretics, ACE inhibitors and antagonists of angiotensin II, FANS, eparine (low molecular weight or not fractionated), cyclosporin, tacrolimus, trimetoprim): the occurrence of hyperpotassemia may depend on the presence of cofactors. The risk of hyperpotassemia is strengthened when the drugs mentioned above are administered simultaneously (see paragraph 4.5). Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see paragraph 4.4). Diuretics: patients who are taking diuretics and, among them, particularly dehydrated patients have a high risk of developing kidney failure resulting in a decrease in kidney blood flow caused by prostaglandin inhibition. These patients must be rehydrated before the start of co-administration and their kidney function must be monitored when the treatment begins (see paragraph 4.4). NSAIDs can reduce the effect of diuretics. ACE inhibitors and antagonists of angiotensin II: in patients with impaired kidney function (e.g. dehydrated patients or elderly patients) co-administration of an ACE inhibitor or an angiotensin II antagonist and agents that inhibit the cyclo-oxidase system may lead to further deterioration of kidney function, which includes a possible acute kidney failure. These interactions must be considered in patients taking KETODOL in conjunction with ACE inhibitors or antagonists of angiotensin II. Therefore, the combination should be given with caution, especially in elderly patients. 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). Metotrexate at 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 slight alterations of kidney function or elderly patients, monitoring must be more frequent. Sulfoniluree: are, moreover, to keep in mind any interactions with oral hypoglycemizers. Pentoxyphylline: increases the risk of bleeding. More careful clinical monitoring and bleeding time monitoring is required. Tenofovir: Concurrent administration of tenofovir disoproxil fumarate and FANS may increase the risk of kidney failure. Cardioactive glycosides: nSAIDs can exacerbate heart failure, reduce glomerular filtration rate and increase heart glycoside levels; however, drug interaction between ketoprofen and cardioactive glycosides has not been demonstrated. ASSOCIATIONS TO CONSIDER Antihypertensives (beta-blockers, inhibitors of angiotensin conversion enzyme, diuretics): risk of decrease in antihypertensive activity (inhibition of vasodilation from prostaglandin caused by NSAs). Trombolitics: increased risk of bleeding. Several substances are involved in interactions due to their anti-aggregating effect: thyrofiban, eptifibatide, abciximab and iloprost. The use of several anti-platelet drugs increases the risk of bleeding. Probenecid: concurrent administration of probenecid can greatly reduce the plasma clearance of ketoprofene. Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal hemorrhage (see paragraph 4.4). Gemeprost: reduced gemeprost effectiveness. Intrauterine contraceptive devices (IUDs): the effectiveness of the device can be reduced resulting in pregnancy. Mifepristone: the effectiveness of the method can, theoretically, be reduced due to the antiprostaglandinic properties of non-steroidal anti-inflammatory drugs (NSAID) including aspirin (acetylsalicylic acid). There are some evidence suggesting that the simultaneous administration of FANS on the day of administration of the dose of prostaglandin does not adversely affect the effects of mifepristone and prostaglandin on cervical maturation or uterine contractility and does not reduce the clinical effectiveness of the medical interruption of pregnancy. Ciclosporine and tacrolimus: contemporary treatment with NSAIDs can lead to the risk of greater nephrotoxicity especially in older individuals. Chinolonic Antibiotics: animal data indicate that NSAIDs can increase the risk of convulsions associated with chinolonic antibiotics. Patients taking NSAIDs and Knolones can have an increased risk of developing seizures. Defenilidantoin and sulfamidic: since the protein bond of ketoprofen is high, it may be necessary to reduce the dose of difenilidantoin or sulfamidics that should be administered simultaneously.

Effects

Like all medicines, KETODOL can cause side effects, although not all people manifest them. 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). Classification of expected frequencies: very common (≥ 1/10); common (from ≥ 1/100 to Emolinfopoietic system pathologies. Rare: anemia due to bleeding, leucopenia; Notable: agranulocytosis, thrombocytopenia, midollar aplasia, hemolytic anemia. Immune system disorders. Notable: anaphylactic reactions (including shock). Disorders of metabolism and nutrition. Notable: hypothoraemia, hyperpotassemia (see paragraphs 4.4 and 4.5). Psychiatric disorders. Notable: depression, hallucinations, confusion, mood alterations, insomnia. Diseases of the nervous system. Not common: headache, dizziness, drowsiness; Rare: paresthesia, discinesia; Notable: asyptic meningitis, seizures, disgeusia. Pathologies of the eye. Rare: blurred vision (see paragraph 4.4). Ear and labyrinth pathologies. Rare: tinnitus, dizziness. Heart disease. Notable: heart failure, atrial fibrillation, palpitations and tachycardia. Vascular diseases. Not known: hypertension, vasodilation, vasculitis (including leukocytoclastic vasculitis). Respiratory, chest and mediastinic pathologies. Rare: asthma attacks, edema of the larynx; Not known: bronchospasm (particularly in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dispnea. Gastrointestinal diseases. The most commonly observed adverse events are gastrointestinal. Common: dyspepsia, nausea, abdominal pain, vomiting, gastralgia, pirosis; Not common: stips, diarrhea, flatulence, gastritis; Rare: ulcerative stomatitis, peptic ulcers, colitis; Notable: exacerbation of colitis and Crohn's disease, perforation or gastrointestinal hemorrhage, sometimes fatal, especially in the elderly (see paragraph 4.4), pancreatitis, melena, ematemesis. The frequency and extent of these effects are significantly reduced by taking the full stomach drug (during meals or with milk). Hepatobiliary diseases. Rare: hepatitis, increased transaminese levels, increased serum bilirubin due to liver disease, jaundice. Pathologies of skin and subcutaneous tissue. Not common: bloodshed, itching; Notable: photosensitization, alopecia, hives, angioedema, erythema, bollose reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, generalized acute urstolosis, dermatitis, eczema. Kidney and urinary pathologies. Not known: abnormality in kidney function tests, acute kidney failure, interstitial tubular nephritis, nephrosic syndrome, dysuria. Systemic pathologies and conditions for administration. Not common: edema, fatigue; Rare: Astenia. Diagnostic examinations. Rare: weight gain. Clinical studies and epidemiological data suggest that the use of NSAIDs (especially high dosages and long-term treatments) may be associated with a modest increase in the risk of arterial thrombotic events (p.es. myocardial infarction and stroke (see paragraph 4.4). Very rare cases of bezoar formation were reported associated with the administration of sucralfate. 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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

Overdosing

Overdose symptoms may include: central nervous system disorders, such as headaches, dizziness, drowsiness, confusion and loss of consciousness, as well as abdominal pain, nausea and vomiting, diarrhea. In case of severe overdose, hypotension, respiratory depression, cyanosis and gastrointestinal bleeding were observed. Overdose cases were reported with doses of up to 2.5 g ketoprofen. In most cases the observed symptoms were benign and limited to letargy, drowsiness, nausea, vomiting and epigastric pain. There are no specific antidotes for overdosing ketoprofen. In the event of a suspicion of severe overdose, gastric lavender and the establishment of support and symptomatic therapies is recommended and to compensate for dehydration, to monitor renal function and to correct acidosis, if present. In case of kidney failure, hemolysis may be useful for removing the medicinal product from the circle.

Pregnancy

: The use of ketoprofen during the first and second trimester of pregnancy must be avoided. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development. Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after the use of an inhibitor of prostaglandin synthesis in the early stages of pregnancy. The absolute risk of heart failure had increased from less than 1% to about 1.5%. It has been estimated that the risk increases with dose and duration of therapy. In animals, the administration of prostaglandin synthesis inhibitors showed an increase in the loss of pre- and post-plant and embryo-fetal mortality. In addition, an increase in the incidence of various malformations, including cardiovascular disorders, was reported in animals that had been given prostaglandin synthesis inhibitors during the organogenetic period. During the first and second trimester of pregnancy KETODOL it should only be used when necessary. If KETODOL is used by women who are trying to have a child or during the first and second trimester of pregnancy, the dose must be as low as possible and the duration of treatment as short as possible. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to: - cardiopulmonary toxicity (with premature closure of arterial duct and pulmonary hypertension); - kidney dysfunction, which can progress in kidney failure with oligoidramnios; the mother and the newborn, at the end of pregnancy, to: - possible prolongation of the bleeding time, and anti-aggregating effect that can also be necessary at very low doses; - inhibition of uterine contractions resulting in delay or extension of labor. The use of the drug in proximity to the childbirth can cause alterations of the hemodynamics of the small circle of the child with serious consequences for breathing. As a result, ketoprofen is contraindicated during the third trimester of pregnancy.

Food

: There is no information available on the excretion of ketoprofen in human milk. Ketoprofen is not recommended during breastfeeding.

Fertility

: The use of NSAIDs can compromise female fertility and is not recommended in women who want to start a pregnancy. In women who have fertility problems or who are subject to fertility investigations, the suspension of treatment must be taken into account.

Source: Farmadati